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Nuciferine inhibits TLR4/NF-κB/MAPK signaling axis and alleviates adjuvant-induced arthritis in rats.
Kulhari, Uttam; Ambujakshan, Anju; Ahmed, Momitul; Washimkar, Kaveri; Kachari, Jodumoni; Mugale, Madhav Nilakanth; Sahu, Bidya Dhar.
Afiliación
  • Kulhari U; Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, 781101, Assam, India.
  • Ambujakshan A; Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, 781101, Assam, India.
  • Ahmed M; Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, 781101, Assam, India.
  • Washimkar K; Toxicology & Experimental Medicine, CSIR-Central Drug Research Institute (CDRI), Lucknow, 226031, India.
  • Kachari J; Department of Veterinary Surgery and Radiology, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, 781022, India.
  • Mugale MN; Toxicology & Experimental Medicine, CSIR-Central Drug Research Institute (CDRI), Lucknow, 226031, India.
  • Sahu BD; Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, 781101, Assam, India. Electronic address: bidyasha@gmail.com.
Eur J Pharmacol ; 982: 176940, 2024 Nov 05.
Article en En | MEDLINE | ID: mdl-39182545
ABSTRACT
Rheumatoid arthritis is an inflammatory condition primarily affecting the joints. Nuciferine (NCF), a key bioactive aporphine alkaloid biosynthesized in lotus leaves, exhibits promising anti-inflammatory and antioxidant properties. In this study, we investigated whether NCF could alleviate inflammatory arthritis conditions in a complete Freund's adjuvant (CFA)-mediated arthritis model in rats. The arthritis model was established through intradermal injection of CFA (100 µL) in the sub-plantar region of the right hind paw. The arthritic animals were treated orally with NCF at 5 and 10 mg/kg and indomethacin (Indo) at 5 mg/kg body weight as reference control. NCF treatment remarkably alleviated inflammatory joint swelling and arthritic index. The radiological and histological analysis revealed evidence of the beneficial effects of NCF. NCF treatment decreased the content of pro-inflammatory cytokines (TNF-α and IL-1ß) and myeloperoxidase (MPO) activity and restored the anti-inflammatory cytokine (IL-10) in the paw joints. The serum levels of pro-inflammatory cytokines were also markedly reduced in the NCF (10 mg/kg) treatment group. Moreover, the arthritis-induced inflammatory mediators, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the toll-like receptor (TLR)-4, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signaling proteins were substantially decreased in the NCF treatment groups. NCF treatment also restored the antioxidant defense enzymes and abrogated lipid peroxidation in the paw tissue. Our findings strongly suggest that NCF is a promising therapeutic molecule for rheumatoid arthritis, inspiring further research, and development in this area.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aporfinas / Artritis Experimental / FN-kappa B / Receptor Toll-Like 4 Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aporfinas / Artritis Experimental / FN-kappa B / Receptor Toll-Like 4 Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos