Nigella sativa L. and its bioactive and nutraceutical components in the management of diabetic peripheral neuropathy.

Nigella sativa L. Black cumin Diabetes Neuropathy Thymoquinone

Journal

Inflammopharmacology
ISSN: 1568-5608
Titre abrégé: Inflammopharmacology
Pays: Switzerland
ID NLM: 9112626

Informations de publication

Date de publication:
14 Aug 2024
Historique:
received: 18 03 2024
accepted: 05 07 2024
medline: 15 8 2024
pubmed: 15 8 2024
entrez: 14 8 2024
Statut: aheadofprint

Résumé

Diabetes-induced hyperglycemia leads to excessive production of oxygen free radicals, inflammatory cytokines, and oxidative stress, which initiates diabetic peripheral neuropathy (DPN). Currently, this condition affects 20% of adults with diabetes. Despite significant advances in the treatment of diabetes, the incidence of its complications, including DPN, is still high. Thus, there is a growing research interest in developing more effective and treatment approaches with less side effects for diabetes and its complications. Nigella sativa L. (NS) has received much research attention as an antioxidant, anti-yperglycemic factor, and anti-inflammatory agent. This natural compound demonstrates its antidiabetic neuropathy effect through various pathways, including the reduction of lipid peroxidation, the enhancement of catalase and superoxide dismutase enzyme activity, and the decrease in inflammatory cytokine levels. The present review focuses on the bioactive and nutraceutical components of black cumin (Nigella sativa L.) and their effects on DPN. In addition, we have also summarized the findings obtained from several experimental and clinical studies regarding the antidiabetic neuropathy effect of NS in animal models and human subjects.

Identifiants

pubmed: 39143432
doi: 10.1007/s10787-024-01528-6
pii: 10.1007/s10787-024-01528-6
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Références

Abbasnezhad A, Niazmand S, Mahmoudabady M, Rezaee SA, Soukhtanloo M, Mosallanejad R et al (2019) Nigella sativa L. seed regulated eNOS, VCAM-1 and LOX-1 genes expression and improved vasoreactivity in aorta of diabetic rat. J Ethnopharmacol 228:142–147
pubmed: 30223051 doi: 10.1016/j.jep.2018.09.021
Abdel-Daim MM, Ghazy EW (2015) Effects of Nigella sativa oil and ascorbic acid against oxytetracycline-induced hepato-renal toxicity in rabbits. Iran J Basic Med Sci 18(3):221
pubmed: 25945233 pmcid: 4414986
Abdel-Daim MM, Shaheen HM, Abushouk AI, Toraih EA, Fawzy MS, Alansari WS et al (2018) Thymoquinone and diallyl sulfide protect against fipronil-induced oxidative injury in rats. Environ Sci Pollut Res 25:23909–23916
doi: 10.1007/s11356-018-2386-3
Abdel-Daim MM, Shaaban Ali M, Madkour FF, Elgendy H (2020) Oral spirulina platensis attenuates hyperglycemia and exhibits antinociceptive effect in streptozotocin-induced diabetic neuropathy rat model. J Pain Res 2:2289–2296
doi: 10.2147/JPR.S267347
Abdel-Daim MM, Abo El-Ela FI, Alshahrani FK, Bin-Jumah M, Al-Zharani M, Almutairi B et al (2020a) Protective effects of thymoquinone against acrylamide-induced liver, kidney and brain oxidative damage in rats. Environ Sci Pollut Res 27:37709–37717
doi: 10.1007/s11356-020-09516-3
Abdel-Daim MM, Abushouk AI, Bungău SG, Bin-Jumah M, El-Kott AF, Shati AA et al (2020b) Protective effects of thymoquinone and diallyl sulphide against malathion-induced toxicity in rats. Environ Sci Pollut Res 27:10228–10235
doi: 10.1007/s11356-019-07580-y
Abdel-Fattah A-FM, Matsumoto K, Watanabe H (2000) Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol 400(1):89–97
pubmed: 10913589 doi: 10.1016/S0014-2999(00)00340-X
Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ (2010) Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic β-cells of streptozotocin-induced diabetic rats. J Diabetes 2(4):256–266
pubmed: 20923501 doi: 10.1111/j.1753-0407.2010.00091.x
Abdelrazek H, Kilany OE, Muhammad MA, Tag HM, Abdelazim AM (2018) Black seed thymoquinone improved insulin secretion, hepatic glycogen storage, and oxidative stress in streptozotocin-induced diabetic male Wistar rats. Oxid Med Cell Longev 20:18
Abel-Salam BK (2012) Immunomodulatory effects of black seeds and garlic on alloxan-induced diabetes in albino rat. Allergol Immunopathol 40(6):336–340
doi: 10.1016/j.aller.2011.07.002
Aboubakr M, Elshafae SM, Abdelhiee EY, Fadl SE, Soliman A, Abdelkader A et al (2021) Antioxidant and anti-inflammatory potential of thymoquinone and lycopene mitigate the chlorpyrifos-induced toxic neuropathy. Pharmaceuticals 14(9):940
pubmed: 34577640 pmcid: 8468258 doi: 10.3390/ph14090940
AbuKhader MM (2013) Thymoquinone in the clinical treatment of cancer: fact or fiction? Pharmacogn Rev 7(14):117
pubmed: 24347919 pmcid: 3841989 doi: 10.4103/0973-7847.120509
Afonseca SOd, Cruz FM, Cubero DdIG, Lera AT, Schindler F, Okawara M et al (2013) Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot randomized clinical trial. Sao Paulo Med J 131:35–38
pubmed: 23538593 pmcid: 10852076 doi: 10.1590/S1516-31802013000100006
Ahlemeyer B, Hühne R, Krieglstein J (2000) Retinoic acid potentiated the protective effect of NGF against staurosporine-induced apoptosis in cultured chick neurons by increasing the trkA protein expression. J Neurosci Res 60(6):767–778
pubmed: 10861789 doi: 10.1002/1097-4547(20000615)60:6<767::AID-JNR9>3.0.CO;2-6
Aisa H, Xin X, Tang D (2019) Nigella sativa: a medicinal and edible plant that ameliorates diabetes. Bioactive Food Diet Interv Diabet. 2:629–640
doi: 10.1016/B978-0-12-813822-9.00040-0
Akhtar MT, Ilyas HF, Shaukat UA, Qadir R, Masood S, Batool S et al (2022) Comparative study of hypoglycaemic and antioxidant potential of methanolic seed extract and oil of Nigella sativa on alloxanized diabetic rabbits. Pak J Pharmac Sci 35:2
Akrom A, Darmawan E (2017) Tolerability and safety of black cumin seed oil (Bcso) administration for 20 days in healthy subjects. Biomed Res 28(9):4196–4201
Al Wafai RJJP (2013) Nigella sativa and thymoquinone suppress cyclooxygenase-2 and oxidative stress in pancreatic tissue of streptozotocin-induced diabetic rats. Pancreas 42(5):841–849
doi: 10.1097/MPA.0b013e318279ac1c
Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA (2008) Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad 20(2):25–27
pubmed: 19385451
Alenezi SKJL (2022) The ameliorative effect of thymoquinone on vincristine-induced peripheral neuropathy in mice by modulating cellular oxidative stress and cytokine. Life 13(1):101
pubmed: 36676049 pmcid: 9860544 doi: 10.3390/life13010101
Al-Ghamdi M (2001) The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 76(1):45–48
pubmed: 11378280 doi: 10.1016/S0378-8741(01)00216-1
Alghobashy AA, Alkholy UM, Talat MA, Abdalmonem N, Zaki A, Ahmed IA et al (2018) Trace elements and oxidative stress in children with type 1 diabetes mellitus. Diabet Metab Syndr Obes Targets Therapy. 2:85–92
doi: 10.2147/DMSO.S157348
Alkhalaf MI, Hussein RH, Hamza A (2020) Green synthesis of silver nanoparticles by Nigella sativa extract alleviates diabetic neuropathy through anti-inflammatory and antioxidant effects. Saudi J Biol Sci 27(9):2410–2419
pubmed: 32884424 pmcid: 7451673 doi: 10.1016/j.sjbs.2020.05.005
Almatroodi SA, Alnuqaydan AM, Alsahli MA, Khan AA, Rahmani AH (2021) Thymoquinone, the most prominent constituent of Nigella sativa, attenuates liver damage in streptozotocin-induced diabetic rats via regulation of oxidative stress, inflammation and cyclooxygenase-2 protein expression. Appl Sci 11(7):3223
doi: 10.3390/app11073223
Amighi J, Sabeti S, Schlager O, Mlekusch W, Exner M, Lalouschek W et al (2004) Low serum magnesium predicts neurological events in patients with advanced atherosclerosis. Stroke 35(1):22–27
pubmed: 14657448 doi: 10.1161/01.STR.0000105928.95124.1F
Anggadiredja K, Kurniati NF (2023) The potential of Nigella sativa oil on clinical output improvement of diabetic neuropathy. J Appl Pharm Sci 13(9):009–017
Ansari MA, Ahmad SJ, Khanum R, Akhtar M (2009) Pharmacological investigation of protective effects of Nigella sativa oil in experimental diabetic neuropathy in rats. Indian J Pharmac Educ Res 43(2):166–176
Apfel SC (1999) Neurotrophic factors in the therapy of diabetic neuropathy. Am J Med 107(2):34–42
doi: 10.1016/S0002-9343(99)00011-X
Apfel SC, Arezzo JC, Lipson L, Kessler JA (1992) Nerve growth factor prevents experimental cisplatin neuropathy. Ann Neurol 31(1):76–80
pubmed: 1543351 doi: 10.1002/ana.410310114
Araújo-Filho HG, Pereira EW, Rezende MM, Menezes PP, Araújo AA, Barreto RS et al (2017) D-limonene exhibits superior antihyperalgesic effects in a β-cyclodextrin-complexed form in chronic musculoskeletal pain reducing fos protein expression on spinal cord in mice. Neuroscience 358:158–169
pubmed: 28673718 doi: 10.1016/j.neuroscience.2017.06.037
Araujo-Filho HG, Pereira EW, Heimfarth L, Monteiro BS, Passos FRS, Siqueira-Lima P et al (2020) Limonene, a food additive, and its active metabolite perillyl alcohol improve regeneration and attenuate neuropathic pain after peripheral nerve injury: evidence for IL-1β TNF-Α, GAP, NGF and ERK involvement. Int Immunopharmacol 86:106766
pubmed: 32652504 doi: 10.1016/j.intimp.2020.106766
Argyriou A, Chroni E, Polychronopoulos P, Iconomou G, Koutras A, Makatsoris T et al (2006) Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced neuropathy. Neurology 67(12):2253–2255
pubmed: 17190958 doi: 10.1212/01.wnl.0000249344.99671.d4
Aristatile B, Al-Assaf AH, Pugalendi KV (2013) Carvacrol suppresses the expression of inflammatory marker genes in D-galactosamine-hepatotoxic rats. Asian Pac J Trop 6(3):205–211
doi: 10.1016/S1995-7645(13)60024-3
Arrieta O, García-Navarrete R, Zuniga S, Ordóñez G, Ortiz A, Palencia G et al (2005) Retinoic acid increases tissue and plasma contents of nerve growth factor and prevents neuropathy in diabetic mice. Eur J Clin Invest 35(3):201–207
pubmed: 15733075 doi: 10.1111/j.1365-2362.2005.01467.x
Arrieta Ó, Hernández-Pedro N, Fernández-González-Aragón M, Saavedra-Pérez D, Campos-Parra A, Rios-Trejo M et al (2011) Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer. Neurology 77(10):987–995
pubmed: 21865574 pmcid: 3171957 doi: 10.1212/WNL.0b013e31822e045c
Arruda VA, de Queiroz GA, Hyslop S, de Araújo PMF, Bon C, de Araújo ALJT (2003) Bothrops lanceolatus (Fer de lance) venom stimulates leukocyte migration into the peritoneal cavity of mice. Toxicon 41(1):99–107
pubmed: 12467667 doi: 10.1016/S0041-0101(02)00238-6
Arruri VK, Gundu C, Kalvala AK, Sherkhane B, Khatri DK, Singh SB (2022) Carvacrol abates NLRP3 inflammasome activation by augmenting Keap1/Nrf-2/p62 directed autophagy and mitochondrial quality control in neuropathic pain. Nutr Neurosci 25(8):1731–1746
pubmed: 33641628 doi: 10.1080/1028415X.2021.1892985
Asemi Z, Karamali M, Jamilian M, Foroozanfard F, Bahmani F, Heidarzadeh Z et al (2015) Retracted: Magnesium supplementation affects metabolic status and pregnancy outcomes in gestational diabetes: a randomized, double-blind, placebo-controlled trial. Elsevier, Amsterdam
doi: 10.3945/ajcn.114.098616
Asle-Rousta M, Amini R, Aghazadeh S (2023) Carvone suppresses oxidative stress and inflammation in the liver of immobilised rats. Arch Physiol Biochem 129(3):597–602
pubmed: 33270467 doi: 10.1080/13813455.2020.1851726
Bach Knudsen KE, Lærke HN, Hedemann MS, Nielsen TS, Ingerslev AK, Gundelund Nielsen DS et al (2018) Impact of diet-modulated butyrate production on intestinal barrier function and inflammation. Nutrients 10(10):1499
pubmed: 30322146 pmcid: 6213552 doi: 10.3390/nu10101499
Badar A, Kaatabi H, Bamosa A, Al-Elq A, Abou-Hozaifa B, Lebda F et al (2017) Effect of Nigella sativa supplementation over a one-year period on lipid levels, blood pressure and heart rate in type-2 diabetic patients receiving oral hypoglycemic agents: nonrandomized clinical trial. Ann Saudi Med 37(1):56–63
pubmed: 28151458 pmcid: 6148980 doi: 10.5144/0256-4947.2017.56
Balbaa M, El-Zeftawy M, Ghareeb D, Taha N, Mandour AW (2016) Nigella sativa relieves the altered insulin receptor signaling in streptozotocin-induced diabetic rats fed with a high-fat diet. Oxid Med Cell Longev 20:16
Balbaa M, Abdulmalek SA, Khalil S (2017) Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: role of Nigella sativa oil and antidiabetic drugs. PLoS ONE 12(5):e0172429
pubmed: 28505155 pmcid: 5432169 doi: 10.1371/journal.pone.0172429
Bamosa AO, Kaatabi H, Lebdaa FM, Elq A-M, Al-Sultanb A (2010) Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Indian J Physiol Pharmacol 54(4):344–354
pubmed: 21675032
Barman S, Pradeep SR, Srinivasan K (2018) Zinc supplementation alleviates the progression of diabetic nephropathy by inhibiting the overexpression of oxidative-stress-mediated molecular markers in streptozotocin-induced experimental rats. J Nutr Biochem 54:113–129
pubmed: 29331868 doi: 10.1016/j.jnutbio.2017.11.008
Baum P, Kosacka J, Estrela-Lopis I, Woidt K, Serke H, Paeschke S et al (2016) The role of nerve inflammation and exogenous iron load in experimental peripheral diabetic neuropathy (PDN). Metabolism 65(4):391–405
pubmed: 26975531 doi: 10.1016/j.metabol.2015.11.002
Beheshti F, Khazaei M, Hosseini MJAjop (2016) Neuropharmacological effects of Nigella sativa. Avic J Phytomed 6(1):104
Bensiameur-Touati K, Kacimi G, Haffaf E-M, Berdja S, Aouichat-Bouguerra S (2017) In vivo subacute toxicity and antidiabetic effect of aqueous extract of Nigella sativa. Evid-Based Complement Alternat Med 20:17
Bhardwaj A, Chaurasia P, Chaturvedi A (2018) A study of magnesium supplementation on sensory nerve conduction velocity (NCV) in patients of diabetic neuropathy. Indian J Clin Anat Physiol 5(3):373–376
Bian S, Gao Y, Zhang M, Wang X, Liu W, Zhang D et al (2013) Dietary nutrient intake and metabolic syndrome risk in Chinese adults: a case–control study. Nutr J 12(1):1–7
doi: 10.1186/1475-2891-12-106
Bilal A, Masud T, Uppal AM, Naveed AK (2009) Effects of Nigella sativa oil on some blood parameters in type 2 diabetes mellitus patients. Asian J Chem 21(7):5373
Binan L, Ajji A, De Crescenzo G, Jolicoeur M (2014) Approaches for neural tissue regeneration. Stem Cell Rev Rep 10:44–59
pubmed: 24092527 doi: 10.1007/s12015-013-9474-z
Bo S, Durazzo M, Guidi S, Carello M, Sacerdote C, Silli B et al (2006) Dietary magnesium and fiber intakes and inflammatory and metabolic indicators in middle-aged subjects from a population-based cohort. Am J Clin Nutr 84(5):1062–1069
pubmed: 17093158 doi: 10.1093/ajcn/84.5.1062
Bonjardim LR, Cunha ES, Guimarães AG, Santana MF, Oliveira MG, Serafini MR et al (2012) Evaluation of the anti-inflammatory and antinociceptive properties of p-cymene in mice. Zeitschrift Für Naturforschung C 67(1–2):15–21
doi: 10.1515/znc-2012-1-203
Boujelben M, Ghorbel F, Vincent C, Makni-Ayadi F, Guermazi F, Croute F et al (2006) Lipid peroxidation and HSP72/73 expression in rat following cadmium chloride administration: interactions of magnesium supplementation. Exp Toxicol Pathol 57(5–6):437–443
pubmed: 16616466 doi: 10.1016/j.etp.2006.02.012
Bouyahya A, Mechchate H, Benali T, Ghchime R, Charfi S, Balahbib A et al (2021) Health benefits and pharmacological properties of carvone. Biomolecules 11(12):1803
pubmed: 34944447 pmcid: 8698960 doi: 10.3390/biom11121803
Bresäter L-E, Welin L, Romanus B (1996) Foot pathology and risk factors for diabetic foot disease in elderly men. Diabet Res Clin Pract 32(1–2):103–109
doi: 10.1016/0168-8227(96)01201-6
Brito RG, Guimarães AG, Quintans JS, Santos MR, De Sousa DP, Badaue-Passos D et al (2012) Citronellol, a monoterpene alcohol, reduces nociceptive and inflammatory activities in rodents. J Nat Med 66:637–644
pubmed: 22350215 doi: 10.1007/s11418-012-0632-4
Britten-Jones AC, Kamel JT, Roberts LJ, Braat S, Craig JP, MacIsaac RJ et al (2021) Investigating the neuroprotective effect of oral omega-3 fatty acid supplementation in type 1 diabetes (nPROOFS1): a randomized placebo-controlled trial. Diabetes 70(8):1794–1806
pubmed: 33952620 doi: 10.2337/db21-0136
Buesing S, Costa M, Schilling JM, Moeller-Bertram T (2019) Vitamin B12 as a treatment for pain. Pain Physician 22(1):E45
pubmed: 30700078 doi: 10.36076/ppj/2019.22.E45
Chausmer AB (1998) Zinc, insulin and diabetes. J Am Coll Nutr 17(2):109–115
pubmed: 9550453 doi: 10.1080/07315724.1998.10718735
Chen L, Li B, Chen B, Shao Y, Luo Q, Shi X et al (2016) Thymoquinone alleviates the experimental diabetic peripheral neuropathy by modulation of inflammation. Sci Rep 6(1):31656
pubmed: 27545310 pmcid: 4992870 doi: 10.1038/srep31656
Chitre NM, Moniri NH, Murnane KS (2019) Omega-3 fatty acids as druggable therapeutics for neurodegenerative disorders. CNS Neurol Disord Drug Targets 18(10):735–749
pubmed: 31724519 pmcid: 7204890 doi: 10.2174/1871527318666191114093749
Cobourne-Duval MK, Taka E, Mendonca P, Bauer D, Soliman (2016) The antioxidant effects of thymoquinone in activated BV-2 murine microglial cells. Neurochem Res 41:3227–3238
pubmed: 27585756 pmcid: 5116410 doi: 10.1007/s11064-016-2047-1
Corcoran J, Maden M (1999) Nerve growth factor acts via retinoic acid synthesis to stimulate neurite outgrowth. Nat Neurosci 2(4):307–308
pubmed: 10204534 doi: 10.1038/7214
Coyle L, Entezaralmahdi M, Adeola M, De Hoyos P, Mehed A, Varon J (2015) The perfect storm: copper deficiency presenting as progressive peripheral neuropathy. Am J Emerg Med 34(2):340
da Silva LM, Quintans-Junior LJ, de Santana WA, Kaneto CM, Soares MBP, Villarreal CFJ (2013) Anti-inflammatory effects of carvacrol: evidence for a key role of interleukin-10. Eur J Pharmacol 699(1):112–117
Dagne E, Bisrat D, Alemayehu M, Worku T (2000) Essential oils of twelve Eucalyptus species from Ethiopia. J Essent Oil Res 12(4):467–470
doi: 10.1080/10412905.2000.9699567
Dai M, Wu L, Yu K, Xu R, Wei Y, Chinnathambi A et al (2020) D-Carvone inhibit cerebral ischemia/reperfusion induced inflammatory response TLR4/NLRP3 signaling pathway. Biomed Pharmacother 132:110870
pubmed: 33080468 doi: 10.1016/j.biopha.2020.110870
Dapino P, Ottonello L, Dallegri FJR (1994) The anti-inflammatory drug nimesulide inhibits neutrophil adherence to and migration across monolayers of cytokine-activated endothelial cells. Respiration 61(6):336–341
pubmed: 7824814 doi: 10.1159/000196365
Darakhshan S, Pour AB, Colagar AH, Sisakhtnezhad (2015) Thymoquinone and its therapeutic potentials. Pharmacol Res 95:138–158
pubmed: 25829334 doi: 10.1016/j.phrs.2015.03.011
Daryabeygi-Khotbehsara R, Golzarand M, Ghaffari MP, Djafarian K (2017) Nigella sativa improves glucose homeostasis and serum lipids in type 2 diabetes: a systematic review and meta-analysis. Complement Ther Med 35:6–13
pubmed: 29154069 doi: 10.1016/j.ctim.2017.08.016
Devaraj S, Cheung AT, Jialal I, Griffen SC, Nguyen D, Glaser N et al (2007) Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications. Diabetes 56(11):2790–2796
pubmed: 17686944 doi: 10.2337/db07-0784
Dibaba DT, Xun P, He K (2014) Dietary magnesium intake is inversely associated with serum C-reactive protein levels: meta-analysis and systematic review. Eur J Clin Nutr 68(4):510–516
pubmed: 24518747 pmcid: 3975661 doi: 10.1038/ejcn.2014.7
Diemel LT, Brewster WJ, Fernyhough P, Tomlinson DR (1994) Expression of neuropeptides in experimental diabetes; effects of treatment with nerve growth factor or brain-derived neurotrophic factor. Mol Brain Res 21(1–2):171–175
pubmed: 7513041 doi: 10.1016/0169-328X(94)90391-3
Doostkam A, Mirkhani H, Iravani K, Karbalay-Doust S, Doosti A, Nadimi E et al (2022) Controversial role of folic acid on diabetic auditory neuropathy. ACS Pharmacol Transl Sci 5(10):985–992
pubmed: 36268113 pmcid: 9578138 doi: 10.1021/acsptsci.2c00140
Durán AM, Beeson WL, Firek A, Cordero-MacIntyre Z, De León M (2022) Dietary omega-3 polyunsaturated fatty-acid supplementation upregulates protective cellular pathways in patients with type 2 diabetes exhibiting improvement in painful diabetic neuropathy. Nutrients 14(4):761
pubmed: 35215418 pmcid: 8876723 doi: 10.3390/nu14040761
Edbladh M, Fex-Svenningsen Å, Ekström P, Edström A (1994) Insulin and IGF-II, but not IGF-I, stimulate the in vitro regeneration of adult frog sciatic sensory axons. Brain Res 641(1):76–82
pubmed: 8019854 doi: 10.1016/0006-8993(94)91817-1
El Rabey HA, Al-Seeni MN, Bakhashwain AS (2017) The antidiabetic activity of Nigella sativa and propolis on streptozotocin-induced diabetes and diabetic nephropathy in male rats. Evid Based Complement Alternat Med 20:17
El-Mahmoudy A, Shimizu Y, Shiina T, Matsuyama H, Nikami H, Takewaki TJAD (2005) Macrophage-derived cytokine and nitric oxide profiles in type I and type II diabetes mellitus: effect of thymoquinone. Acta Diabetol 42:23–30
pubmed: 15868110 doi: 10.1007/s00592-005-0170-6
Emerit J, Beaumont C, Trivin F (2001) Iron metabolism, free radicals, and oxidative injury. Biomed Pharmacother 55(6):333–339
pubmed: 11478586 doi: 10.1016/S0753-3322(01)00068-3
Engelen W, Bouten A, De Leeuw I, De Block C (2000) Are low magnesium levels in type 1 diabetes associated with electromyographical signs of polyneuropathy? Magnes Res 13(3):197–203
pubmed: 11008927
Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 23(5):599–622
pubmed: 12372842 doi: 10.1210/er.2001-0039
Faizal A, Geelen DJP (2013) Saponins and their role in biological processes in plants. Phytochem Rev 12:877–893
doi: 10.1007/s11101-013-9322-4
Faradji V, Sotelo J (1990) Low serum levels of nerve growth factor in diabetic neuropathy. Acta Neurol Scand 81(5):402–406
pubmed: 2375241 doi: 10.1111/j.1600-0404.1990.tb00984.x
Fararh K, Atoji Y, Shimizu Y, Shiina T, Nikami H, Takewaki T (2004) Mechanisms of the hypoglycaemic and immunopotentiating effects of Nigella sativa L. oil in streptozotocin-induced diabetic hamsters. Res Vet Sci 77(2):123–129
pubmed: 15196902 doi: 10.1016/j.rvsc.2004.03.002
Farvid MS, Homayouni F, Amiri Z, Adelmanesh F (2011) Improving neuropathy scores in type 2 diabetic patients using micronutrients supplementation. Diabetes Res Clin Pract 93(1):86–94
pubmed: 21496936 doi: 10.1016/j.diabres.2011.03.016
Forouzanfar F, Hosseinzadeh H (2018) Medicinal herbs in the treatment of neuropathic pain: a review. Iran J Basic Med Sci 21(4):347–358
pubmed: 29796216 pmcid: 5960749
Fouad IA, Sharaf NM, Abdelghany RM, El Sayed NS (2018) Neuromodulatory effect of thymoquinone in attenuating glutamate-mediated neurotoxicity targeting the amyloidogenic and apoptotic pathways. Front Neurol 9:236
pubmed: 29706929 pmcid: 5908889 doi: 10.3389/fneur.2018.00236
Freitas AC, Peigneur S, Macedo FH, Menezes-Filho JE, Millns P, Medeiros LF et al (2018) The peptide PnPP-19, a spider toxin derivative, activates μ-opioid receptors and modulates calcium channels. Toxins 10(1):43
pubmed: 29342943 pmcid: 5793130 doi: 10.3390/toxins10010043
Fricker RA, Green EL, Jenkins SI, Griffin SM (2018) The influence of nicotinamide on health and disease in the central nervous system. Int J Tryptophan Res 11:1178646918776658
pubmed: 29844677 pmcid: 5966847 doi: 10.1177/1178646918776658
Galicia-Moreno M, Lucano-Landeros S, Monroy-Ramirez HC, Silva-Gomez J, Gutierrez-Cuevas J, Santos A et al (2020) Roles of Nrf2 in liver diseases: molecular, pharmacological, and epigenetic aspects. Antioxidants 9(10):980
pubmed: 33066023 pmcid: 7601324 doi: 10.3390/antiox9100980
Galisteo M, Duarte J, Zarzuelo A (2008) Effects of dietary fibers on disturbances clustered in the metabolic syndrome. J Nutr Biochem 19(2):71–84
pubmed: 17618108 doi: 10.1016/j.jnutbio.2007.02.009
Gan Z-S, Wang Q-Q, Li J-H, Wang X-L, Wang Y-Z, Du H-H (2017) Iron reduces M1 macrophage polarization in RAW2647 macrophages associated with inhibition of STAT1. Mediat Inflam 20:17
Garland H (1992) New experimental data on the relationship between diabetes mellitus and magnesium. Magnes Res 5(3):193–202
pubmed: 1467158
Gasperi V, Sibilano M, Savini I, Catani MV (2019) Niacin in the central nervous system: an update of biological aspects and clinical applications. Int J Mol Sci 20(4):974
pubmed: 30813414 pmcid: 6412771 doi: 10.3390/ijms20040974
Gholamnezhad Z, Keyhanmanesh R, Boskabady MH (2015) Anti-inflammatory, antioxidant, and immunomodulatory aspects of Nigella sativa for its preventive and bronchodilatory effects on obstructive respiratory diseases: a review of basic and clinical evidence. J Funct Foods 17:910–927
doi: 10.1016/j.jff.2015.06.032
Ghosh S, Bhattacharyya S, Rashid K, Sil PC (2015) Curcumin protects rat liver from streptozotocin-induced diabetic pathophysiology by counteracting reactive oxygen species and inhibiting the activation of p53 and MAPKs mediated stress response pathways. Toxicol Rep 2:365–376
pubmed: 28962370 pmcid: 5598222 doi: 10.1016/j.toxrep.2014.12.017
Grothey A (2005) Clinical management of oxaliplatin-associated neurotoxicity. Clin Colorectal Cancer 5:S38–S46
pubmed: 15871765 doi: 10.3816/CCC.2005.s.006
Guan W, Ni Z, Hu Y, Liang W, Ou C, He J et al (2020) Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382(18):1708–1720
pubmed: 32109013 doi: 10.1056/NEJMoa2002032
Guo Y, Han X, Che H, Li Z, Dong P, Xue C et al (2018) Synergistic effect of eicosapentaenoic acid-enriched phospholipids and sea cucumber saponin on orotic acid-induced non-alcoholic fatty liver disease in rats. R Soc Open Sci 5(7):172182
pubmed: 30109054 pmcid: 6083717 doi: 10.1098/rsos.172182
Gupta R, Garg V, Mathur D, Goyal R (1998) Oral zinc therapy in diabetic neuropathy. J Assoc Physicians India 46(11):939–942
pubmed: 11229219
Hadi S, Mirmiran P, Hadi V, Hosseinpour-Niazi S, Emamat SM (2016) Effects of Nigella sativa on cardiovascular risk factors. J Mazandaran Univ Med Sci 25(134):430–442
Hajhashemi V, Ghannadi A, Jafarabadi H (2004) Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phytother Res 18(3):195–199
pubmed: 15103664 doi: 10.1002/ptr.1390
Hamdy NM, Taha RA (2009) Effects of Nigella sativa oil and thymoquinone on oxidative stress and neuropathy in streptozotocin-induced diabetic rats. Pharmacology 84(3):127–134
pubmed: 19684436 doi: 10.1159/000234466
Haupt E, Ledermann H, Köpcke W (2005) Benfotiamine in the treatment of diabetic. Int J Clin Pharmacol Ther 43(2):71–77
pubmed: 15726875 doi: 10.5414/CPP43071
Hayakawa K, Itoh T, Niwa H, Mutoh T, Sobue G (1998) NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule: In vitro study of adult rat sympathetic ganglion explants. Brain Res 794(2):313–319
pubmed: 9622663 doi: 10.1016/S0006-8993(98)00305-9
Hayee M, Mohammad Q, Haque A (2005) Diabetic neuropathy and zinc therapy. Bangl Med Res Counc Bull 31(2):62–67
Held S, Schieberle P, Somoza VJJ (2007) Characterization of α-terpineol as an anti-inflammatory component of orange juice by in vitro studies using oral buccal cells. J Agric Food Chem 55(20):8040–8046
pubmed: 17867636 doi: 10.1021/jf071691m
Hellweg R, Hartung HD (1990) Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: a possible role for NGF in the pathogenesis of diabetic neuropathy. J Neurosci Res 26(2):258–267
pubmed: 2142224 doi: 10.1002/jnr.490260217
Herder C, Peltonen M, Koenig W, Sütfels K, Lindström J, Martin S et al (2009) Anti-inflammatory effect of lifestyle changes in the Finnish Diabetes Prevention Study. Diabetologia 52:433–442
pubmed: 19130041 doi: 10.1007/s00125-008-1243-1
Hernández-Pedro N, Ordóñez G, Ortiz-Plata A, Palencia-Hernández G, García-Ulloa AC, Flores-Estrada D et al (2008) All-trans retinoic acid induces nerve regeneration and increases serum and nerve contents of neural growth factor in experimental diabetic neuropathy. Transl Res 152(1):31–37
pubmed: 18593635 doi: 10.1016/j.trsl.2008.05.007
Hernández-Pedro N, Granados-Soto V, Ordoñez G, Pineda B, Rangel-López E, Salazar-Ramiro A et al (2014) Vitamin A increases nerve growth factor and retinoic acid receptor beta and improves diabetic neuropathy in rats. Transl Res 164(3):196–201
pubmed: 24768685 doi: 10.1016/j.trsl.2014.04.002
Hotta M, Nakata R, Katsukawa M, Hori K, Takahashi S, Inoue HJ (2010) Carvacrol, a component of thyme oil, activates PPARα and γ and suppresses COX-2 expression [S]. J Lip Res 51(1):132–139
doi: 10.1194/jlr.M900255-JLR200
Hurt JK, Coleman JL, Fitzpatrick BJ, Taylor-Blake B, Bridges AS, Vihko P et al (2012) Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine. PLoS ONE 7(10):e48562
pubmed: 23119057 pmcid: 3485352 doi: 10.1371/journal.pone.0048562
Hussein RM, Mohamed WR, Omar HAJPB (2018) A neuroprotective role of kaempferol against chlorpyrifos-induced oxidative stress and memory deficits in rats via GSK3β-Nrf2 signaling pathway. Physiology 152:29–37
Hussein M, Fathy W, Hassan A, Elkareem RA, Marzouk S, Kamal YS (2021) Zinc deficiency correlates with severity of diabetic polyneuropathy. Brain Behav 11(10):e2349
pubmed: 34521153 pmcid: 8553312 doi: 10.1002/brb3.2349
Javidi S, Razavi BM (2016) A review of neuropharmacology effects of nigella sativa and its main component. Thymoquinone 30(8):1219–1229
Jayaraj RL, Azimullah S, Parekh KA, Ojha SK, Beiram RJH (2022) Effect of citronellol on oxidative stress, neuroinflammation and autophagy pathways in an in vivo model of Parkinson’s disease. Heliyon 8:11
doi: 10.1016/j.heliyon.2022.e11434
Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi R, Constantine G, Katulanda P (2012) Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr 4(1):1–12
doi: 10.1186/1758-5996-4-13
Jeddi M, Torabi E (2019) The Relationship between Zinc, glycemic control and microvascular complications of diabetes mellitus. Int J Nutr Sci 4(3):130–136
Ji R-R, Samad TA, Jin S-X, Schmoll R, Woolf CJ (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36(1):57–68
pubmed: 12367506 doi: 10.1016/S0896-6273(02)00908-X
Jrah Harzallah H, Grayaa R, Kharoubi W, Maaloul A, Hammami M, Mahjoub T (2012) Thymoquinone, the Nigella sativa bioactive compound, prevents circulatory oxidative stress caused by 1, 2-dimethylhydrazine in erythrocyte during colon postinitiation carcinogenesis. Oxid Med Cell Longev 20:12
Kaatabi H, Bamosa AO, Badar A, Al-Elq A, Abou-Hozaifa B, Lebda F et al (2015) Nigella sativa improves glycemic control and ameliorates oxidative stress in patients with type 2 diabetes mellitus: placebo controlled participant blinded clinical trial. PLoS ONE 10(2):e0113486
pubmed: 25706772 pmcid: 4338020 doi: 10.1371/journal.pone.0113486
Kaimoto T, Hatakeyama Y, Takahashi K, Imagawa T, Tominaga M, Ohta TJEJP (2016) Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene. Eur J Pain 20(7):1155–1165
pubmed: 27030509 doi: 10.1002/ejp.840
Kalamegam G, Alfakeeh SM, Bahmaid AO, AlHuwait EA, Gari MA, Abbas MM et al (2020) In vitro evaluation of the anti-inflammatory effects of thymoquinone in osteoarthritis and in silico analysis of inter-related pathways in age-related degenerative diseases. Front Cell Dev Biol 8:646
pubmed: 32793594 pmcid: 7391788 doi: 10.3389/fcell.2020.00646
Kanter M (2008) Effects of Nigella sativa and its major constituent, thymoquinone on sciatic nerves in experimental diabetic neuropathy. Neurochem Res 33:87–96
pubmed: 17713854 doi: 10.1007/s11064-007-9419-5
Kanter M, Meral I, Yener Z, Ozbek H, Demir H (2003) Partial regeneration/proliferation of the β-cells in the Islets of Langerhans by Nigella sativa L. in streptozotocin-induced diabetic rats. Tohoku J Exp Med 201(4):213–219
pubmed: 14690013 doi: 10.1620/tjem.201.213
Kanter M, Akpolat M, Aktas C (2009) Protective effects of the volatile oil of Nigella sativa seeds on β-cell damage in streptozotocin-induced diabetic rats: a light and electron microscopic study. J Mol Histol 40:379–385
pubmed: 20049514 doi: 10.1007/s10735-009-9251-0
Kara M, Uslu S, Demirci F, Temel HE, Baydemir CJI (2015) Supplemental carvacrol can reduce the severity of inflammation by influencing the production of mediators of inflammation. Inflammation 38:1020–1027
pubmed: 25416233 doi: 10.1007/s10753-014-0066-0
Karandrea S, Yin H, Liang X, Slitt AL, Heart EA (2017) Thymoquinone ameliorates diabetic phenotype in diet-induced obesity mice via activation of SIRT-1-dependent pathways. PLoS ONE 12(9):e0185374
pubmed: 28950020 pmcid: 5614580 doi: 10.1371/journal.pone.0185374
Kazemi M (2015) Chemical composition and antioxidant properties of the essential oil of Nigella sativa L. Bangl J Bot 44(1):111–116
doi: 10.3329/bjb.v44i1.22732
Khodaie S-A, Nikkhah H, Namiranian N, Abotorabi M, Askari M, Khalilzadeh SH et al (2023) Topical Nigella sativa L. product: a new candidate for the management of diabetic peripheral neuropathy. Inflammopharmacology 2:1–9
Kim K, Song Y, Oh TJ, Choi SH, Jang HC (2020) Association between iron intake and diabetic peripheral neuropathy in type 2 diabetes: significance of iron intake and the ratio between iron intake and polyunsaturated fatty acids intake. Nutrients 12(11):3365
pubmed: 33139615 pmcid: 7693683 doi: 10.3390/nu12113365
Kohandel Z, Farkhondeh T, Aschner M, Samarghandian S (2021) Anti-inflammatory effects of thymoquinone and its protective effects against several diseases. Biomed Pharmacother 138:111492
pubmed: 33743334 doi: 10.1016/j.biopha.2021.111492
Kooti W, Hasanzadeh-Noohi Z, Sharafi-Ahvazi N, Asadi-Samani M, Ashtary-Larky DJC (2016) Phytochemistry, pharmacology, and therapeutic uses of black seed (Nigella sativa). Chin J Nat Med 14(10):732–745
pubmed: 28236403
Kopruszinski CM, Reis RC, Bressan E, Reeh PW, Chichorro JG (2015) Vitamin B complex attenuated heat hyperalgesia following infraorbital nerve constriction in rats and reduced capsaicin in vivo and in vitro effects. Eur J Pharmacol 762:326–332
pubmed: 26048309 doi: 10.1016/j.ejphar.2015.05.063
Kottschade LA, Sloan JA, Mazurczak MA, Johnson DB, Murphy BP, Rowland KM et al (2011) The use of vitamin E for the prevention of chemotherapy-induced peripheral neuropathy: results of a randomized phase III clinical trial. Support Care Cancer 19:1769–1777
pubmed: 20936417 doi: 10.1007/s00520-010-1018-3
Kowluru A, Chen H-Q, Modrick LM, Stefanelli C (2001) Activation of acetyl-CoA carboxylase by a glutamate-and magnesium-sensitive protein phosphatase in the islet β-cell. Diabetes 50(7):1580–1587
pubmed: 11423479 doi: 10.2337/diabetes.50.7.1580
Kundu JK, Liu L, Shin J-W, Surh Y-JJB, Communications B (2013) Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo. Biochem Biophys Res Commun 438(4):721–727
pubmed: 23911786 doi: 10.1016/j.bbrc.2013.07.110
Kwon WY, Suh GJ, Kim KS, Lee HJ, Jeong KY, Kwak YH et al (2013) Niacin suppresses the mitogen-activated protein kinase pathway and attenuates brain injury after cardiac arrest in rats. Crit Care Med 41(9):e223–e232
pubmed: 23648567 doi: 10.1097/CCM.0b013e31828a2394
Lane JT (2014) The role of retinoids in the induction of nerve growth factor: a potential treatment for diabetic neuropathy. Transl Res 164(3):193–195
pubmed: 24995388 doi: 10.1016/j.trsl.2014.06.001
Lavle N, Shukla P, Panchal AJJPS, Research B (2016) Role of flavonoids and saponins in the treatment of diabetes mellitus 6(4):535–41
Leinninger GM, Edwards JL, Lipshaw MJ, Feldman EL (2006) Mechanisms of disease: mitochondria as new therapeutic targets in diabetic neuropathy. Nat Clin Pract Neurol 2(11):620–628
pubmed: 17057749 doi: 10.1038/ncpneuro0320
Lewis EJ, Perkins BA, Lovblom LE, Bazinet RP, Wolever TM, Bril V (2017) Effect of omega-3 supplementation on neuropathy in type 1 diabetes: a 12-month pilot trial. Neurology 88(24):2294–2301
pubmed: 28515269 pmcid: 5567321 doi: 10.1212/WNL.0000000000004033
Lewis EJ, Lovblom LE, Cisbani G, Chen DK, Bazinet RP, Wolever TM et al (2021) Baseline omega-3 level is associated with nerve regeneration following 12-months of omega-3 nutrition therapy in patients with type 1 diabetes. J Diabet Compl 35(3):107798
doi: 10.1016/j.jdiacomp.2020.107798
Liu Y, Guo Y, Wang Z (2007) Effect of magnesium on reactive oxygen species production in the thigh muscles of broiler chickens. Br Poult Sci 48(1):84–89
pubmed: 17364545 doi: 10.1080/00071660601148187
Liu F, Ma F, Kong G, Wu K, Deng Z, Wang H (2014) Zinc supplementation alleviates diabetic peripheral neuropathy by inhibiting oxidative stress and upregulating metallothionein in peripheral nerves of diabetic rats. Biol Trace Elem Res 158:211–218
pubmed: 24615552 doi: 10.1007/s12011-014-9923-9
Loram L, Fuller A, Fick L, Cartmell T, Poole S (2007) Cytokine profiles during carrageenan-induced inflammatory hyperalgesia in rat muscle and hind paw. J Pain 8(2):127–136
pubmed: 16949880 doi: 10.1016/j.jpain.2006.06.010
Mahmoodi MR, Mohammadizadeh M (2020) Therapeutic potentials of Nigella sativa preparations and its constituents in the management of diabetes and its complications in experimental animals and patients with diabetes mellitus: a systematic review. Complement Ther Med 50:102391
pubmed: 32444053 doi: 10.1016/j.ctim.2020.102391
Mansi KS (2006) Effects of oral administration of water extract of Nigella sativa on the hypothalamus pituitary adrenal axis in experimental diabetes. Int J Pharmacol 2(1):104–109
doi: 10.3923/ijp.2006.104.109
Mashayekhi-Sardoo H, Rezaee R, Karimi G (2018) An overview of in vivo toxicological profile of thymoquinone. Toxin Rev 2:5
Mazur A, Maier JA, Rock E, Gueux E, Nowacki W, Rayssiguier Y (2007) Magnesium and the inflammatory response: potential physiopathological implications. Arch Biochem Biophys 458(1):48–56
pubmed: 16712775 doi: 10.1016/j.abb.2006.03.031
Menezes RR, Godin AM, Rodrigues FF, Coura GM, Melo IS, Brito AMS et al (2017) Thiamine and riboflavin inhibit production of cytokines and increase the anti-inflammatory activity of a corticosteroid in a chronic model of inflammation induced by complete Freund’s adjuvant. Pharmacol Rep 69(5):1036–1043
pubmed: 28958614 doi: 10.1016/j.pharep.2017.04.011
Migdalis I, Triantafilou P, Petridou E, Varvarigos N, Totolos V, Rigopoulos A (2005) Lipid peroxides in type 2 diabetic patients with neuropathy. Res Commun Mol Pathol Pharmacol 117:5–12
pubmed: 18426075
Moalem SA, Hosseinzadeh H, Farahi S (2008) A study of acute and chronic anti-nociceptive and anti-inflammatory effects of thiamine in mice
Mocchegiani E, Giacconi R, Malavolta M (2008) Zinc signalling and subcellular distribution: emerging targets in type 2 diabetes. Trends Mol Med 14(10):419–428
pubmed: 18774338 doi: 10.1016/j.molmed.2008.08.002
Mohamed WS, Mostafa AM, Mohamed KM, Serwah AH (2015) Effects of fenugreek, Nigella, and termis seeds in nonalcoholic fatty liver in obese diabetic albino rats. Arab J Gastroenterol 16(1):1–9
pubmed: 25670619 doi: 10.1016/j.ajg.2014.12.003
Moreira M, Cruz G, Lopes M, Albuquerque A, Leal-Cardoso JJBJM (2001) Effects of terpineol on the compound action potential of the rat sciatic nerve. Braz J Med Biol Res 34:1337–1340
pubmed: 11593310 doi: 10.1590/S0100-879X2001001000015
Moses T, Papadopoulou KK, Osbourn AJC (2014) Metabolic and functional diversity of saponins, biosynthetic intermediates and semi-synthetic derivatives. Crit Rev Biochem Mol Biol 49(6):439–462
pubmed: 25286183 pmcid: 4266039 doi: 10.3109/10409238.2014.953628
Muruganathan U, Srinivasan SJB (2016) Beneficial effect of carvone, a dietary monoterpene ameliorates hyperglycemia by regulating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats. Pharmacotherapy 84:1558–1567
doi: 10.1016/j.biopha.2016.11.025
Nazıroğlu M, Yürekli VA (2013) Effects of antiepileptic drugs on antioxidant and oxidant molecular pathways: focus on trace elements. Cell Mol Neurobiol 33:589–599
pubmed: 23584684 doi: 10.1007/s10571-013-9936-5
Negi P, Rathore C, Sharma G, Singh B, Katare OPJR (2018) Thymoquinone a potential therapeutic molecule from the plant Nigella sativa: role of colloidal carriers in its effective delivery. Recent Patents Drug Deliv Formul 12(1):3–22
doi: 10.2174/1872211311666171129121128
Nesterkina M, Barbalat D, Konovalova I, Shishkina S, Atakay M, Salih B et al (2021) Novel (-)-carvone derivatives as potential anticonvulsant and analgesic agents. Nat Prod Res 35(23):4978–4987
pubmed: 32336164 doi: 10.1080/14786419.2020.1756804
Newsholme P, Keane KN, Carlessi R, Cruzat V (2019) Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: importance to cell metabolism, function, and dysfunction. Am J Physiol Cell Physiol 317(3):C420–C433
pubmed: 31216193 doi: 10.1152/ajpcell.00141.2019
Nicol GD, Vasko MR (2007) Unraveling the story of NGF-mediated sensitization of nociceptive sensory neurons: ON or OFF the Trks? Mol Interv 7(1):26
pubmed: 17339604 doi: 10.1124/mi.7.1.6
Nielsen FH, Johnson LK, Zeng H (2010) Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Magnes Res 23(4):158–168
pubmed: 21199787
Niero M, Bartoli G, De Colle P, Scarcella M, Zanetti M (2023) Impact of dietary fiber on inflammation and insulin resistance in older patients: a narrative review. Nutrients 15(10):2365
pubmed: 37242248 pmcid: 10220584 doi: 10.3390/nu15102365
Noor N, Mourad IJJAS (2010) Evaluation of antioxidant effect of Nigella sativa oil on monosodium glutamate-induced oxidative stress in rat brain. J Am Sci 6:139
Ojo AB, Adanlawo IG, Ojo OAJIJPPR (2017) Efficacy of saponins from Helianthus annuus roots on antihyperglycemic antiperoxidative and antihyperlipidemic effects in alloxan-induced diabetic rats. Phytochem Res 9:83–88
Ojo O, Feng Q-Q, Ojo OO, Wang X-H (2020) The role of dietary fibre in modulating gut microbiota dysbiosis in patients with type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Nutrients 12(11):3239
pubmed: 33113929 pmcid: 7690692 doi: 10.3390/nu12113239
Oliveira Y, Jm MA, Nzenze J (2013) Copper deficiency and peripheral neuropathy as an outcome of gastrectomy. La Revue De Med Int 34(4):234–236
doi: 10.1016/j.revmed.2012.12.019
Omar NM, Atia GM (2012) Effect of Nigella sativa on pancreatic β-cell damage in streptozotocin-induced diabetic rats: histological and immunohistochemical study. Egypt J Histol 35(1):106–116
doi: 10.1097/01.EHX.0000411475.79484.90
Omidi H, Khorram S, Mesgari M, Asghari-Jafarabadi M, Tarighat-Esfanjani A (2017) Effects of separate and concurrent supplementation of Nano-sized clinoptilolite and Nigella sativa on oxidative stress, anti-oxidative parameters and body weight in rats with type 2 diabetes. Biomed Pharmacother 96:1335–1340
pubmed: 29169727 doi: 10.1016/j.biopha.2017.11.077
Ordoñez G, Fernandez A, Perez R, Sotelo J (1994) Low contents of nerve growth factor in serum and submaxillary gland of diabetic mice: a possible etiological element of diabetic neuropathy. J Neurol Sci 121(2):163–166
pubmed: 8158209 doi: 10.1016/0022-510X(94)90346-8
Oskouei Z, Akaberi M, Hosseinzadeh H (2018) A glance at black cumin (Nigella sativa) and its active constituent, thymoquinone, in ischemia: a review. Iran J Basic Med Sci 21(12):1200
pubmed: 30627362 pmcid: 6312681
Ozaydin D, Bektasoglu P, Koyuncuoglu T, Ozkaya S, Koroglu A, Akakin D et al (2023) Anti-inflammatory, antioxidant and neuroprotective effects of niacin on mild traumatic brain injury in rats. Turk Neurosurg 33:6
Padhye S, Banerjee S, Ahmad A, Mohammad R, Sarkar FHJCt, (2008) From here to eternity-the secret of pharaohs: therapeutic potential of black cumin seeds and beyond. Cancer Therapy 6:495
pubmed: 19018291 pmcid: 2583426
Padhye S, Banerjee S, Ahmad A, Mohammad R, Sarkar FH (2008) From here to eternity-the secret of pharaohs: therapeutic potential of black cumin seeds and beyond. Cancer Therapy 6:495
pubmed: 19018291 pmcid: 2583426
Paeschke S, Baum P, Toyka KV, Blüher M, Koj S, Klöting N et al (2019) The role of iron and nerve inflammation in diabetes mellitus type 2-induced peripheral neuropathy. Neuroscience 406:496–509
pubmed: 30867132 doi: 10.1016/j.neuroscience.2019.03.005
Paez-Hurtado A, Calderon-Ospina C, Nava-Mesa M (2023) Mechanisms of action of vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) in pain: a narrative review. Nutr Neurosci 26(3):235–253
pubmed: 35156556 doi: 10.1080/1028415X.2022.2034242
Pari L, Sankaranarayanan C (2009) Beneficial effects of thymoquinone on hepatic key enzymes in streptozotocin–nicotinamide induced diabetic rats. Life Sci 85(23–26):830–834
pubmed: 19903489 doi: 10.1016/j.lfs.2009.10.021
Park SB, Goldstein D, Lin CSY, Krishnan AV, Friedlander ML, Kiernan MC (2009) Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. J Clin Oncol 27(8):1243–1249
pubmed: 19164207 doi: 10.1200/JCO.2008.19.3425
Pathan H (2012) Basic opioid pharmacology: an update. Br J Pain 6(1):11–16
pubmed: 26516461 pmcid: 4590096 doi: 10.1177/2049463712438493
Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C (2013) Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci 14(11):21525–21550
pubmed: 24177571 pmcid: 3856020 doi: 10.3390/ijms141121525
Pop-Busui R, Low PA, Waberski BH, Martin CL, Albers JW, Feldman EL et al (2009) Effects of prior intensive insulin therapy on cardiac autonomic nervous system function in type 1 diabetes mellitus: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC). Circulation 119(22):2886–2893
pubmed: 19470886 pmcid: 2757005 doi: 10.1161/CIRCULATIONAHA.108.837369
Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA et al (2017) Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care 40(1):136
pubmed: 27999003 doi: 10.2337/dc16-2042
Purves T, Middlemas A, Agthong S, Jude EB, Boulton AJ, Fernyhough P et al (2001) A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy. FASEB J 15(13):2508–2514
pubmed: 11689477 doi: 10.1096/fj.01-0253hyp
Pyridoxine-related peripheral neuropathy.
Quintans-Júnior LJ, Oliveira MG, Santana MF, Santana MT, Guimarães AG, Siqueira JS et al (2011) α-Terpineol reduces nociceptive behavior in mice. Pharmac Biol 49(6):583–586
doi: 10.3109/13880209.2010.529616
Rahmani AH, Aly S (2015) Nigella sativa and its active constituents thymoquinone shows pivotal role in the diseases prevention and treatment. Saudi Med J 8(1):48–53
Ramsay R, Ciznadija D, Vanevski M, Mantamadiotis TJ (2003) Transcriptional regulation of cyclo-oxygenase expression: three pillars of control. Pharmacology 16(2):59–67
Razzaghi R, Pidar F, Momen-Heravi M, Bahmani F, Akbari H, Asemi Z (2018) Magnesium supplementation and the effects on wound healing and metabolic status in patients with diabetic foot ulcer: a randomized, double-blind, placebo-controlled trial. Biol Trace Elem Res 181:207–215
pubmed: 28540570 doi: 10.1007/s12011-017-1056-5
Richard D, Kefi K, Barbe U, Bausero P, Visioli F (2008) Polyunsaturated fatty acids as antioxidants. Pharmacol Res 57(6):451–455
pubmed: 18583147 doi: 10.1016/j.phrs.2008.05.002
Richardsen E, Uglehus RD, Due J, Busch C, Busund L-T (2010) COX-2 is overexpressed in primary prostate cancer with metastatic potential and may predict survival. A comparison study between COX-2, TGF-β, IL-10 and Ki67. Cancer Epidemiol 34(3):316–322
pubmed: 20409773 doi: 10.1016/j.canep.2010.03.019
Rodrı́guez-Morán M Guerrero-Romero F (2001) Low serum magnesium levels and foot ulcers in subjects with type 2 diabetes. Arch Med Res 32(4):300–303
pubmed: 11440788 doi: 10.1016/S0188-4409(01)00298-3
Said G (2007) Diabetic neuropathy—a review. Nat Clin Pract Neurol 3(6):331–340
pubmed: 17549059 doi: 10.1038/ncpneuro0504
Saif MW, Reardon J (2005) Management of oxaliplatin-induced peripheral neuropathy. Ther Clin Risk Manag 1(4):249–258
pubmed: 18360567 pmcid: 1661634
Sakai C, Ishida M, Ohba H, Yamashita H, Uchida H, Yoshizumi M et al (2017) Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells. PLoS ONE 12(11):e0187934
pubmed: 29121093 pmcid: 5679535 doi: 10.1371/journal.pone.0187934
Salama RHM (2011) Hypoglycemic effect of lipoic acid, carnitine and Nigella sativa in diabetic rat model. Int J Health Sci 5(2):126
Salazar MO, Osella MI, Arcusin DE, Lescano LE, Furlan RL (2020) New α-glucosidase inhibitors from a chemically engineered essential oil of Origanum vulgare L. Ind Crops Prod 156:112855
doi: 10.1016/j.indcrop.2020.112855
Salem ML (2005) Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol 5(13–14):1749–1770
pubmed: 16275613 doi: 10.1016/j.intimp.2005.06.008
Sallehuddin N, Nordin A, Fauzi MBJ (2020) Nigella sativa and its active compound, thymoquinone, accelerate wound healing in an in vivo animal model: a comprehensive review. Int J Environ Res Public Health 17(11):4160
pubmed: 32545210 pmcid: 7312523 doi: 10.3390/ijerph17114160
Salvemini D, Wang ZQ, Wyatt PS, Bourdon DM, Marino MH, Manning PT et al (1996) Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br J Pharmacol 118(4):829–838
pubmed: 8799551 pmcid: 1909531 doi: 10.1111/j.1476-5381.1996.tb15475.x
Sánchez-Ramírez GM, Caram-Salas NL, Rocha-González HI, Vidal-Cantú GC, Medina-Santillán R, Reyes-García G et al (2006) Benfotiamine relieves inflammatory and neuropathic pain in rats. Eur J Pharmacol 530(1–2):48–53
pubmed: 16359659 doi: 10.1016/j.ejphar.2005.11.016
Sangi SMA, Bawadekji A, Al AM (2018) Comparative effects of metformin, Pleurotus ostreatus, Nigella Sativa, and Zingiber officinale on the streptozotocin-induced diabetes mellitus in rats. Pharmacogn Mag 14(Suppl 1):S268–S273
doi: 10.4103/pm.pm_108_18
Sango K, Verdes JM, Hikawa N, Horie H, Tanaka S, Inoue S et al (1994) Nerve growth factor (NGF) restores depletions of calcitonin gene-related peptide and substance P in sensory neurons from diabetic mice in vitro. J Neurol Sci 126(1):1–5
pubmed: 7530767 doi: 10.1016/0022-510X(94)90087-6
Santos PL, Rabelo TK, Matos JP, Anjos KS, Melo MA, Carvalho YM et al (2021) Involvement of nuclear factor κB and descending pain pathways in the anti-hyperalgesic effect of β-citronellol, a food ingredient, complexed in β-cyclodextrin in a model of complex regional pain syndrome-Type 1. Food Chem Toxicol 153:112260
pubmed: 34051299 doi: 10.1016/j.fct.2021.112260
Santos WB, Pina LT, de Oliveira MA, Santos LA, Batista MV, Trindade GG et al (2023) Antinociceptive effect of a p-cymene/β-cyclodextrin inclusion complex in a murine cancer pain model: characterization aided through a docking study. Molecules 28(11):4465
pubmed: 37298941 pmcid: 10254339 doi: 10.3390/molecules28114465
Seker U, Kaya S, Kandemir SI, Sener D, Demirel OU, Nergiz Y eds (2022) Effects of black cumin seed oil on oxidative stress and expression of membrane-cytoskeleton linker proteins, radixin, and moesin in streptozotocin-induced diabetic rat liver. Hepatology Forum; Turkish Association for the Study of the Liver
Sengupta A, Das S, Maji D, De M, Biswas P, Chakraborty AK (2018) Balance between antioxidant enzyme and lipid peroxidation in diabetes neuropathy. Balance 3(2):1125–1128
Severina II, Severin FF, Korshunova GA, Sumbatyan NV, Ilyasova TM, Simonyan RA et al (2013) In search of novel highly active mitochondria-targeted antioxidants: thymoquinone and its cationic derivatives. FEBS Lett 587(13):2018–2024
pubmed: 23665033 doi: 10.1016/j.febslet.2013.04.043
Shinomiya M, Kawamura K, Tanida E, Nagoshi M, Motoda H, Kasanami Y et al (2012) Neurite outgrowth of PC12 mutant cells induced by orange oil and d-limonene via the p38 MAPK pathway. Acta Med Okayama 66(2):111–118
pubmed: 22525469
Shrivastava R, Agrawal R, Parveen ZJJCCS (2011) A review on therapeutic applications of Nigella sativa. J Chem Chem Sci 1(4):241–248
Shu G (2012) Use of volatile oil from plants in preparing medicaments for preventing and treating diabetes. Google Patent
Singh R, Farooq SA, Mannan A, Singh TG, Najda A, Grażyna Z et al (2022) Animal models of diabetic microvascular complications: relevance to clinical features. Biomed Pharmacother 145:112305
pubmed: 34872802 doi: 10.1016/j.biopha.2021.112305
Sjöberg J, Kanje M (1989) Insulin-like growth factor (IGF-1) as a stimulator of regeneration in the freeze-injured rat sciatic nerve. Brain Res 485(1):102–108
pubmed: 2720394 doi: 10.1016/0006-8993(89)90671-9
Skaper SD (2012) The neurotrophin family of neurotrophic factors: an overview. Neurotroph Fact Methods Protoc 2:1–12
Sloan G, Selvarajah D, Tesfaye S (2021) Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy. Nat Rev Endocrinol 17(7):400–420
pubmed: 34050323 doi: 10.1038/s41574-021-00496-z
Sobhi W, Khettal B, Belmouhoub M, Atmani D, Duez P, Benboubetra M (2011) Hepatotoxicity and Langerhans islets regenerative effects of polar and neutral lipids of Nigella sativa L. in nicotinamide/streptozotocin-induced diabetic rats. Pteridines 22(1):97–104
doi: 10.1515/pteridines.2011.22.1.97
Soleimani M, Sheikholeslami MA, Ghafghazi S, Pouriran R, Parvardeh SJ (2019) Analgesic effect of α-terpineol on neuropathic pain induced by chronic constriction injury in rat sciatic nerve: involvement of spinal microglial cells and inflammatory cytokines. Iran J Basic Med Sci 22(12):1445
pubmed: 32133063 pmcid: 7043874
Soltani N, Nematbakhsh M, Eshraghi-Jazi F, Talebi A, Ashrafi F (2013) Effect of oral administration of magnesium on Cisplatin-induced nephrotoxicity in normal and streptozocin-induced diabetic rats. Nephro-Urol Monthly 5(4):884
doi: 10.5812/numonthly.11624
Song Y, Manson JE, Buring JE, Liu S (2004) Dietary magnesium intake in relation to plasma insulin levels and risk of type 2 diabetes in women. Diabetes Care 27(1):59–65
pubmed: 14693967 doi: 10.2337/diacare.27.1.59
Song X-S, Huang Z-J, Song X-J (2009) Thiamine suppresses thermal hyperalgesia, inhibits hyperexcitability, and lessens alterations of sodium currents in injured, dorsal root ganglion neurons in rats. J Am Soc Anesthesiol 110(2):387–400
doi: 10.1097/ALN.0b013e3181942f1e
Soundharrajan I, Kim DH, Srisesharam S, Kuppusamy P, Sivanesan R, Choi KCJP (2018) Limonene promotes osteoblast differentiation and 2-deoxy-d-glucose uptake through p38MAPK and Akt signaling pathways in C2C12 skeletal muscle cells. Phytomedicine 45:41–48
pubmed: 29573911 doi: 10.1016/j.phymed.2018.03.019
Srinivasan S, Muruganathan UJC (2016) Antidiabetic efficacy of citronellol, a citrus monoterpene by ameliorating the hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Chem-Biol Interact 250:38–46
pubmed: 26944432 doi: 10.1016/j.cbi.2016.02.020
Stroud S, Salvato P, Thompson C (eds) (1994) Magnesium level and peripheral neuropathy. International Conference on AIDS Int Conf AIDS
Tang L-Y, Heller M, Meng Z, Yu L-R, Tang Y, Zhou M et al (2017) Transforming growth factor-β (TGF-β) directly activates the JAK1-STAT3 axis to induce hepatic fibrosis in coordination with the SMAD pathway. J Biol Chem 292(10):4302–4312
pubmed: 28154170 pmcid: 5354477 doi: 10.1074/jbc.M116.773085
Tavakkoli A, Hosseinzadeh H (2020) Nigella sativa L. and thymoquinone as neuroprotective antioxidants. Oxidative stress and dietary antioxidants in neurological diseases. Elsevier, Amsterdam, pp 325–341
doi: 10.1016/B978-0-12-817780-8.00021-9
Tewari S, Salman M, Thadani S, Singh S, Ahmad A (2015) A study of pregabalin, tramadol, their combination and Nigella sativa in neuropathic pain in rats. Int J Pharm Sci Res 6(10):4406
Thomas JP, Bachowski GJ, Girotti AW (1986) Inhibition of cell membrane lipid peroxidation by cadmium-and zinc-metallothioneins. Biochim Biophys Acta Gen Subj 884(3):448–461
doi: 10.1016/0304-4165(86)90195-9
Thomazzi S, Silva C, Silveira D, Vasconcellos C, Lira A, Cambui E et al (2010) Antinociceptive and anti-inflammatory activities of Bowdichia virgilioides (sucupira). J Ethnopharmacol 127(2):451–456
pubmed: 19837149 doi: 10.1016/j.jep.2009.10.014
Tolonen M (1990) Vitamins and minerals in health and nutrition. Elsevier, Amsterdam
Tosiello L (1996) Hypomagnesemia and diabetes mellitus: a review of clinical implications. Arch Intern Med 156(11):1143–1148
pubmed: 8639008 doi: 10.1001/archinte.1996.00440100029005
Veronese N, Watutantrige-Fernando S, Luchini C, Solmi M, Sartore G, Sergi G et al (2016) Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials. Eur J Clin Nutr 70(12):1354–1359
pubmed: 27530471 doi: 10.1038/ejcn.2016.154
Weickert MO, Pfeiffer AF (2008) Metabolic effects of dietary fiber consumption and prevention of diabetes. J Nutr 138(3):439–442
pubmed: 18287346 doi: 10.1093/jn/138.3.439
Widodo GP, Herowati R, Perangin-Angin JM, Kamlasi J (2016) Antihyperglycemic, antioxidant, and pancreas regeneration activities of black cumin (Nigella sativa L.) seeds ethanol extract in alloxan-induced diabetic rats. Int J Pharm Pharmac Sci 8(5):37–40
Winkler G, Pál B, Nagybégányi E, Öry I, Porochnavec M, Kempler P (1999) Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy. Arzneimittelforschung 49(03):220–224
pubmed: 10219465
Xu J, Wang S, Feng T, Chen Y, Yang GJ, Medicine M (2018) Hypoglycemic and hypolipidemic effects of total saponins from Stauntonia chinensis in diabetic db/db mice. J Cell Mol Med 22(12):6026–6038
pubmed: 30324705 pmcid: 6237556 doi: 10.1111/jcmm.13876
Yang XD, Fang PF, Xiang DX, Yang YY (2019) Topical treatments for diabetic neuropathic pain. Exp Ther Med 17(3):1963–1976
pubmed: 30783472 pmcid: 6364237
Yazdi HB, Hojati V, Shiravi A, Hosseinian S, Vaezi G (2019) Liver dysfunction and oxidative stress in streptozotocin-induced diabetic rats: protective role of Artemisia turanica. J Pharmacopunc 22(2):109
doi: 10.3831/KPI.2019.22.014
Yilmaz M, Aktug H, Oltulu F, Erbas O (2016) Neuroprotective effects of folic acid on experimental diabetic peripheral neuropathy. Toxicol Ind Health 32(5):832–840
pubmed: 24311627 doi: 10.1177/0748233713511513
Yimer EM, Tuem KB, Karim A, Ur-Rehman N, Anwar F (2019) Nigella sativa L (black cumin): a promising natural remedy for wide range of illnesses. Evid-Based Complement Alternat Med 20:19
Yorek MA (2018) The potential role of fatty acids in treating diabetic neuropathy. Curr DiabRep 18:1–10
Zaoui A, Cherrah Y, Lacaille-Dubois M, Settaf A, Amarouch H, Hassar M (2000) Diuretic and hypotensive effects of Nigella sativa on the spontaneously hypertensive rat. Therapie 55(3):379–382
pubmed: 10967716
Zargar AH, Shah NA, Masoodi SR, Laway BA, Dar FA, Khan AR et al (1998) Copper, zinc, and magnesium levels in non-insulin dependent diabetes mellitus. Postgrad Med J 74(877):665–668
pubmed: 10197198 pmcid: 2431594 doi: 10.1136/pgmj.74.877.665
Zhang M-M, Sun L-L, Li C, Gao W, Yang J-B, Wang A-G et al (2014) A new lanostane-type triterpenoid from Cymbopogon citratus. China J Chin Mater Med 39(10):1834–1837
Zhao S, Zhang L, Xu Z, Chen W (2013) Neurotoxic effects of iron overload under high glucose concentration. Neural Regen Res 8(36):3423
pubmed: 25206665 pmcid: 4146010
Ziaee T, Moharreri N, Hosseinzadeh HJJoMP (2012) Review of pharmacological and toxicological effects of Nigella sativa and its active constituents. 11(42):16–42
Zielińska M, Dereń K, Polak-Szczybyło E, Stępień AE (2021) The role of bioactive compounds of Nigella sativa in rheumatoid arthritis therapy—current reports. Nutrients 13(10):3369
pubmed: 34684370 pmcid: 8539759 doi: 10.3390/nu13103369

Auteurs

Seyed-Ali Khodaie (SA)

Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Roghaye Razavi (R)

Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Haniyeh Nikkhah (H)

Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Nasim Namiranian (N)

Community & Preventive Medicine, Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Mohammad Kamalinejad (M)

School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. mkamalinejad@yahoo.com.
Behdane Baran Salem Abi Company, Tehran, Iran. mkamalinejad@yahoo.com.
AB Pharma inc267 Esplanade West, North Vancouver, BC, Canada. mkamalinejad@yahoo.com.

Classifications MeSH