Dose–Response Analgesic and Anti-Inflammatory Effects of a De-Oiled Saffron Petal Fraction in Diabetic Neuropathic Pain
Keywords:
saffron petals, diabetic neuropathy, analgesia, inflammation, dose response, oxidative stressAbstract
Background: Diabetic neuropathic pain involves peripheral sensitisation, inflammatory activation and oxidative injury. Saffron petals are an underused botanical by-product containing potentially bioactive compounds.
Objective: To define the dose–response profile of a de-oiled saffron-petal fraction in experimental diabetic neuropathy.
Methods: Diabetes was induced in 72 rats and neuropathy confirmed four weeks later using mechanical and thermal testing. Animals were randomised to vehicle, three extract doses, pregabalin or non-diabetic control. Treatments continued for 21 days. Behavioural outcomes were measured serially, while sciatic-nerve oxidative markers, TNF-α, IL-1β and histomorphometry were assessed at study end.
Results: The 200 mg/kg dose produced the most consistent response, increasing mechanical withdrawal thresholds by 52% from pretreatment values and prolonging thermal withdrawal latency by 39%. The 400 mg/kg dose did not provide additional behavioural benefit. Compared with diabetic controls, the 200 mg/kg group showed lower malondialdehyde, higher glutathione and superoxide-dismutase activity, and reduced TNF-α and IL-1β concentrations. Histological scoring demonstrated less axonal degeneration and endoneurial oedema. No clinically meaningful changes in alanine aminotransferase, creatinine or body weight were observed across treatment groups.
Conclusion: A mid-range dose of the de-oiled saffron-petal fraction produced the best balance of analgesic, anti-inflammatory and antioxidant effects in diabetic neuropathy. The non-linear dose response highlights the need for chemical standardisation and pharmacokinetic work before translational studies.
Publication format: research abstract. No full-text manuscript accompanies this record.
References
Alam SR, Nasrin N, Chowdhury NS, Akter R, Rahman MA, Chowdhury RN, Tahsin MR, Arnob TA, Morshed N, Mia MSH, Opo FADM, Aktar F, Miah MM, Büyüker SM, Reza R, Ayubee MS, Reza MS, Chowdhury JA, Chowdhury AA, Kabir S, Amran MS. Exploring the abundance of de-oiled non-resin analgesic and anti-inflammatory compounds in Crocus sativus through polarity-directed quaternary solvent extraction in both diabetic and non-diabetic conditions: Integrating in silico and in vivo analysis. Acta Pharm Sci. 2026;64(2):181-232. doi:10.23893/1307-2080.APS64012.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-254.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2^-Delta Delta CT method. Methods. 2001;25(4):402-408.
Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132(3):344-362.
Ma Q. Role of Nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol. 2013;53:401-426.
Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol. 2015;4:180-183.
Forman HJ, Maiorino M, Ursini F. Signaling functions of reactive oxygen species. Biochemistry. 2010;49(5):835-842.
Nathan C, Ding A. Nonresolving inflammation. Cell. 2010;140(6):871-882.
Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454(7203):428-435.
Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860-867.
Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98-107.
Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Res. 2007;125(3):451-472.
OECD. Test No. 425: Acute Oral Toxicity: Up-and-Down Procedure. OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2008.
Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717.
Banerjee P, Kemmler E, Dunkel M, Preissner R. ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2024;52(W1):W513-W520.
Hollingsworth SA, Dror RO. Molecular dynamics simulation for all. Neuron. 2018;99(6):1129-1143.
Genheden S, Ryde U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin Drug Discov. 2015;10(5):449-461.
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-461.
Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008;4(11):682-690.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498-2504.
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage. Nucleic Acids Res. 2019;47(D1):D607-D613.
Srivastava R, Ahmed H, Dixit RK, Dharamveer, Saraf SA. Crocus sativus L.: a comprehensive review. Pharmacogn Rev. 2010;4(8):200-208.
Melnyk JP, Wang S, Marcone MF. Chemical and biological properties of the world's most expensive spice: saffron. Food Res Int. 2010;43(8):1981-1989.
Hosseinzadeh H, Nassiri-Asl M. Avicenna's (Ibn Sina) the Canon of Medicine and saffron (Crocus sativus): a review. Phytother Res. 2013;27(4):475-483.
Abdullaev FI. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med. 2002;227(1):20-25.
Bukhari SI, Manzoor M, Dhar MK. A comprehensive review of the pharmacological potential of Crocus sativus and its bioactive apocarotenoids. Biomed Pharmacother. 2018;98:733-745.
Pop-Busui R, Boulton AJM, Feldman EL, Bril V, Freeman R, Malik RA, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136-154.
Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5(1):41.
Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11(6):521-534.
Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3:17002.
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