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. 2025 Apr;33(4):2109-2128.
doi: 10.1007/s10787-025-01703-3. Epub 2025 Mar 11.

The action of injectable nanodispersion of Bixa orellana (Chronic-in®) on arthritis in diabetic rats: pharmacological and histopathological studies

Lauana Gomes  1 , Helison de Oliveira Carvalho  1 , Gisele Rocha Lopes  1 , Gabriel da Costa Furtado  1 , Danna Emanuelle Santos Gonçalves  1 , Nayara Nilcia Dias Colares  1 , Adriana Maciel Ferreira  1 , Crislany da Costa Furtado  1 , Heitor Ribeiro da Silva  1 , Abrahão Victor Tavares de L T Dos Santos  1   2 , Aline Lopes do Nascimento  1   2 , Tamiris Marques Lage  1 , Irma Danielle Rodrigues Pedro  1 , Thiago Afonso Teixeira  1   2   3 , José Carlos Tavares Carvalho  4   5   6
Affiliations

The action of injectable nanodispersion of Bixa orellana (Chronic-in®) on arthritis in diabetic rats: pharmacological and histopathological studies

Lauana Gomes et al. Inflammopharmacology. 2025 Apr.

Abstract

Diabetic arthritis (DA) is a microvascular complication associated with diabetes mellitus (DM), necessitating the exploration of innovative therapeutic approaches. The Amazon biome, rich in bioactive compounds, offers potential treatments; notably, Bixa orellana, which contains tocotrienol and geranylgeraniol, exhibits anti-inflammatory and antioxidant properties, particularly when formulated as a nanodispersion.

Objective: This study aims to investigate the pharmacological effects of an injectable nanodispersion of Bixa orellana, termed Chronic-in®, in diabetic Wistar rats.

Method: Male Wistar rats were employed in the study, and DA was induced using an intraperitoneal injection of 100 mg/kg alloxan and an intraplantar administration of Freund's complete adjuvant. The animals were divided into five groups (n = 5): CON (normal rats treated with saline solution IM), CHR SC (DA rats treated with Chronic-in SC daily), SS (DA rats treated with saline solution IM), IND (DA rats treated with indomethacin orally), and CHR IM (DA rats treated with Chronic-in IM every 3 days). Treatment outcomes were assessed through various parameters, including changes in paw edema, Arthritic Index (AI), performance in the open field and Rotarod tests, radiographic evaluations using the Eichenholtz classification, Scanning Electron Microscopy (SEM) analysis of articular morphology, and hematological and biochemical assessments.

Results: Significant reductions in edema were observed in the CHR SC, CHR IM, and IND groups (p < 0.001) compared to the SSA group. The AI showed significant differences among the CON, CHR SC, and CHR IM groups. Enhanced exploratory behavior was noted in the open field test for the Chronic-in-treated groups, particularly with IM administration. The Rotarod test demonstrated marked differences between the Chronic-in-treated, CON and SS groups. Radiographic and SEM evaluations indicated fewer bone alterations in the CHR IM and SC groups compared to the SSA and IND groups, along with preservation of articular surfaces. Histological assessments revealed thickened synovial membranes and pannus formation in the SS and IND groups. In contrast, CHR IM and CHR SC groups exhibited minimal loss of proteoglycans akin to the CON group.

Conclusion: Treatment with Chronic-in via both IM and SC routes effectively mitigated the inflammatory manifestations of diabetic neuropathic arthritis, demonstrating lower pain intensity during ambulation and protective effects against inflammation and joint integrity as evidenced in histological analyses. These findings suggest that Chronic-in represents a promising therapeutic option for diabetic arthritis.

Keywords: Arthritis; Diabetes; Injectable nanodispersion; Nanocomposites.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that there are no conflicts of interest.

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