A promising impact of oral administration of noscapine against imiquimod-induced psoriasis-like skin lesions

Document Type : Original Research Article

Authors

1 Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Cardiovascular Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective: Psoriasis is a chronic inflammatory autoimmune disease. The effectiveness of noscapine has been employed as a helpful treatment for various disorders and subjected to recent theoretical breakthroughs.
Materials and Methods: Psoriasis-like lesions were induced by topical application of 5% imiquimod (IMQ) (10 mg/cm2 of skin) in male Balb/c mice and then medicated with a single oral dose of methotrexate (MET) as a positive control or daily oral treatment of noscapine (5, 15 and 45 mg/kg). In this way, skin inflammation intensity, psoriatic itchiness, psoriasis area severity index (PASI) score, ear length, thickness, and organ weight were daily measured. At the end of the study, histological and immunohistochemical and enzyme-linked immunosorbent assays (ELISA, for pro-/anti-inflammatory factors) were performed in each ear.
Results: IMQ caused psoriasis-like lesions. Noscapine markedly alleviated macroscopic parameters, namely ear thickness, ear length, skin inflammation, itching, and organ weight, as well as microscopic parameters including, pathology and Ki67 and p53, and tissue immunological mediators, such as tumour necrosis factor (TNF-α), interleukin (IL)-10, transforming growth factor (TGF-β), interferon-g (IFN-g), IL-6, IL-17, and IL-23p19 in the psoriatic skin in a concentration manner (p<0.05-<0.001).
Conclusion: Therefore, noscapine with good pharmacological properties has considerable effects on psoriasis inflammation.

Keywords


Alexander SPH, Roberts RE, Broughton BRS,
Sobey CG, George CH, Stanford SC,
Cirino G, Docherty JR, Giembycz MA,
Hoyer D, Insel PA, Izzo AA, Ji Y,
MacEwan DJ, Mangum J, Wonnacott S,
Ahluwalia A. 2018. Goals and practicalities
of immunoblotting and
immunohistochemistry: A guide for
submission to the British Journal of
Pharmacology. Br J Pharmacol, 175: 407-
411.
Askari VR, Baradaran Rahimi V, Assaran A,
Iranshahi M, Boskabady MH. 2020.
Evaluation of the anti-oxidant and antiinflammatory effects of the methanolic
extract of Ferula szowitsiana root on PHAinduced inflammation in human
lymphocytes. Drug Chem Toxicol, 43: 353-
360.
Askari VR, Baradaran Rahimi V, Tabatabaee
SA, Shafiee-Nick R. 2019. Combination of
imipramine, a sphingomyelinase inhibitor,
and beta-caryophyllene improve their
therapeutic effects on experimental
autoimmune encephalomyelitis (EAE). Int
Immunopharmacol, 77: 105923.
Baradaran Rahimi V, Rajabian A, Rajabi H,
Mohammadi Vosough E, Mirkarimi HR,
Hasanpour M, Iranshahi M, Rakhshandeh
H, Askari VR. 2020. The effects of hydroethanolic extract of Capparis spinosa (C.
spinosa) on lipopolysaccharide (LPS)-
induced inflammation and cognitive
impairment: Evidence from in vivo and in
vitro studies. J Ethnopharmacol, 256:
112706.
Benhadou F, Mintoff D, Del Marmol V. 2019.
Psoriasis: keratinocytes or immune cells–
which is the trigger? Dermatology, 235: 91-
100.
Bischoff KB, Dedrick RL, Zaharko DS,
Longstreth JA. 1971. Methotrexate
pharmacokinetics. J Pharm Sci, 60: 1128-
1133.
Bradford MM. 1976. A rapid and sensitive
method for the quantitation of microgram
quantities of protein utilizing the principle
of protein-dye binding. Anal Biochem, 72:
248-254.
Chan ES, Cronstein BN. 2010. Methotrexate—
how does it really work? Nat Rev
Rheumatol, 6: 175-178.
Chen X, Dang TT, Facchini PJ. 2015.
Noscapine comes of age. Phytochemistry,
111: 7-13.
Chiricozzi A, Romanelli P, Volpe E,
Borsellino G, Romanelli M. 2018.
Scanning the immunopathogenesis of
psoriasis. Int J Mol Sci, 19: 179.
Conrad C, Gilliet M. 2018. Psoriasis: from
pathogenesis to targeted therapies. Clin Rev
Allergy Immunol, 54: 102-113.
Curtis MJ, Bond RA, Spina D, Ahluwalia A,
Alexander SP, Giembycz MA, Gilchrist A,
Hoyer D, Insel PA, Izzo AA. 2015.
Experimental design and analysis and their
reporting: new guidance for publication in
BJP. Br J Pharmacol, 172: 3461-3471.
Dahlström B, Mellstrand T, Löfdahl C-G,
Johansson M. 1982. Pharmakokinetic
Oral noscapine reduces psoriasis lesion
AJP, Vol. 13, No. 4, Jul-Aug 2023 427
properties of noscapine. Eur J Clin
Pharmacol, 22: 535-539.
Deng Y, Chang C, Lu Q. 2016. The
inflammatory response in psoriasis: a
comprehensive review. Clin Rev Allergy
Immunol, 50: 377-389.
Desai PR, Marepally S, Patel AR, Voshavar C,
Chaudhuri A, Singh M. 2013. Topical
delivery of anti-TNFalpha siRNA and
capsaicin via novel lipid-polymer hybrid
nanoparticles efficiently inhibits skin
inflammation in vivo. J Control Release,
170: 51-63.
Di Meglio P, Villanova F, Nestle FO. 2014.
Psoriasis. Cold Spring Harb Perspect Med,
4: a015354.
Dubois Declercq S, Pouliot R. 2013.
Promising new treatments for psoriasis.
ScientificWorldJournal, 2013: 980419.
Ebrahimi SA. 2020. Noscapine, a possible
drug candidate for attenuation of cytokine
release associated with SARS-CoV-2. Drug
Dev Res, 81: 765-767.
Farhangian ME, Feldman SR. 2015.
Immunogenicity of biologic treatments for
psoriasis: therapeutic consequences and the
potential value of concomitant
methotrexate. Am J Clin Dermatol, 16:
285-294.
Furue M, Furue K, Tsuji G, Nakahara T. 2020.
Interleukin-17A and keratinocytes in
psoriasis. Int J Mol Sci, 21: 1275.
George CH, Stanford SC, Alexander S, Cirino
G, Docherty JR, Giembycz MA, Hoyer D,
Insel PA, Izzo AA, Ji Y, MacEwan DJ,
Sobey CG, Wonnacott S, Ahluwalia A.
2017. Updating the guidelines for data
transparency in the British Journal of
Pharmacology - data sharing and the use of
scatter plots instead of bar charts. Br J
Pharmacol, 174: 2801-2804.
Harden JL, Krueger JG, Bowcock AM. 2015.
The immunogenetics of psoriasis: a
comprehensive review. J Autoimmun, 64:
66-73.
Hawkes JE, Yan BY, Chan TC, Krueger JG.
2018. Discovery of the IL-23/IL-17
signaling pathway and the treatment of
psoriasis. J Immunol, 201: 1605-1613.
Michalek IM, Loring B, John SM. 2017. A
systematic review of worldwide
epidemiology of psoriasis. J Eur Acad
Dermatol Venereol, 31: 205-212.
Na Takuathung M, Wongnoppavich A,
Panthong A, Khonsung P, Chiranthanut N,
Soonthornchareonnon N, Sireeratawong S.
2018. Antipsoriatic effects of wannachawee
recipe on imiquimod-induced psoriasis-like
dermatitis in balb/c mice. Evid Based
Complement Alternat Med, 2018: 7931031.
Nourbakhsh F, Askari VR. 2021. Biological
and pharmacological activities of
noscapine: focusing on its receptors and
mechanisms. BioFactors, 47: 975-991.
Nourbakhsh F, Mousavi SH, RahmanianDevin P, Baradaran Rahimi V,
Rakhshandeh H, Askari VR. 2022. Topical
formulation of noscapine, a
benzylisoquinoline alkaloid, ameliorates
imiquimod-induced psoriasis-like skin
lesions. Evid Based Complement Alternat
Med, 2022: 3707647.
Parisi R, Symmons DP, Griffiths CE, Ashcroft
DM. Global epidemiology of psoriasis: a
systematic review of incidence and
prevalence. J Invest Dermatol, 133: 377-
385.
Rahmanian-Devin P, Baradaran Rahimi V,
Jaafari MR, Golmohammadzadeh S, SaneiFar Z, Askari VR. 2021a. Noscapine, an
emerging medication for different diseases:
a mechanistic review. Evid Based
Complement Alternat Med, 2021: 8402517.
Rahmanian-Devin P, Rakhshandeh H,
Baradaran Rahimi V, Sanei-Far Z,
Hasanpour M, Memarzia A, Iranshahi M,
Askari VR. 2021b. Intraperitoneal lavage
with Crocus sativus prevents postoperativeinduced peritoneal adhesion in a rat model:
evidence from animal and cellular studies.
Oxid Med Cell Longev, 2021: 5945101.
Rendon A, Schakel K. 2019. Psoriasis
pathogenesis and treatment. Int J Mol Sci,
20: 1475.
Roenigk HH, Auerbach R, Maibach HI,
Weinstein GD. 1988. Methotrexate in
psoriasis: revised guidelines. J Am Acad
Dermatol, 19: 145-156.
Sakai K, Sanders KM, Youssef MR,
Yanushefski KM, Jensen L, Yosipovitch G,
Akiyama T. 2016. Mouse model of
imiquimod-induced psoriatic itch. Pain,
157: 2536-2543.
Sakai K, Sanders KM, Youssef MR,
Yanushefski KM, Jensen LE, Yosipovitch
G, Akiyama T. 2017. Role of neurturin in
spontaneous itch and increased
nonpeptidergic intraepidermal fiber density
in a mouse model of psoriasis. Pain, 158:
2196-2202.
Nourbakhsh et al.
AJP, Vol. 13, No. 4, Jul-Aug 2023 428
Sukal SA, Nadiminti L, Granstein RD. 2006.
Etanercept and demyelinating disease in a
patient with psoriasis J Am Acad Dermatol,
54: 160-164.
Sun J, Zhao Y, Hu J. 2013. Curcumin inhibits
imiquimod-induced psoriasis-like
inflammation by inhibiting IL-1beta and
IL-6 production in mice. PloS One, 8:
e67078.
Sung B, Ahn KS, Aggarwal BB. 2010.
Noscapine, a benzylisoquinoline alkaloid,
sensitizes leukemic cells to
chemotherapeutic agents and cytokines by
modulating the NF-kappaB signaling
pathway. Cancer Res, 70: 3259-3268.
Szepietowski JC, Reich A, Wisnicka B. 2002.
Itching in patients suffering from psoriasis.
Acta Dermatovenerol Croat, 10: 221-226.
Tomar V, Kukreti S, Prakash S, Madan J,
Chandra R. 2017. Noscapine and its
analogs as chemotherapeutic agent: Current
updates. Curr Top Med Chem, 17: 174-188.
Van Der Fits L, Mourits S, Voerman JS, Kant
M, Boon L, Laman JD, Cornelissen F, Mus
A-M, Florencia E, Prens EP. 2009.
Imiquimod-induced psoriasis-like skin
inflammation in mice is mediated via the
IL-23/IL-17 axis. J Immunol, 182: 5836-
5845.
Wu JJ, Nguyen TU, Poon KY, Herrinton LJ.
2012. The association of psoriasis with
autoimmune diseases. J Am Acad
Dermatol, 67: 924-930.
Zhang M, Li N, Cai R, Gu J, Xie F, Wei H, Lu
C, Wu D. 2021. Rosmarinic acid protects
mice from imiquimod induced psoriasislike skin lesions by inhibiting the IL23/Th17 axis via regulating Jak2/Stat3
signaling pathway. Phytother Res, 35:
4526-4537