Intra-Articular Route for the System of Molecules 14G1862 from Centella Asiatica: Pain Relieving and Protective Effects in a Rat Model of Osteoarthritis.

Laura Micheli,Luisa Mattoli,Carla Ghelardini,Sara Tamimi,Cristina Luceri,Emiliano Giovagnoni,Enrico Flamini,Lorenzo Cinci,Mario D’Ambrosio,Lorenzo Di Cesare Mannelli,Jacopo Lucci,Stefano Garetto

doi:10.3390/nu12061618

Abstract

Current pharmacological therapies for the management of chronic articular diseases are far from being satisfactory, so new strategies need to be investigated. We tested the intra-articular pain relieving properties of a system of molecules from a characterized Centella asiatica extract (14G1862) in a rat model of osteoarthritis induced by monoiodoacetate (MIA). 14G1862 (0.2–2 mg mL−1) was intra-articularly (i.a.) injected 7 days after MIA, behavioural and histological evaluations were performed 14, 30 and 60 days after treatments. Moreover, the effect of 14G1862 on nitrate production and iNOS expression in RAW 264.7 macrophages stimulated with LPS was assessed. In vitro, 14G1862 treatment attenuated LPS-induced NO production and iNOS expression in a comparable manner to celecoxib. In vivo, 14G1862 significantly reduced mechanical allodynia and hyperalgesia, spontaneous pain and motor alterations starting on day 14 up to day 60. The efficacy was higher or comparable to that evoked by triamcinolone acetonide (100 μg i.a.) used as reference drug. Histological evaluation highlighted the improvement of several morphological parameters in MIA + 14G1862-treated animals with particularly benefic effects on joint space and fibrin deposition. In conclusion, i.a. treatment with Centella asiatica is a candidate to be a novel effective approach for osteoarthritis therapy.

Highlights

Osteoarthritis (OA) is a chronic degenerative joint disease typically affecting the knee, hips, fingers, and/or lower spinal regions [1] and is clinically characterized by gradual development of fluctuating joint pain, swelling, stiffness, and loss of motion [2]
The results obtained showed how potent the analytical approach used to determine the molecular composition of 14G1862
Using different techniques principally based on mass spectrometry, ninety-three organic compounds, 24 elements and 4 anions were successfully identified from 14G1862, achieving a comprehensive chemical characterization of the system of molecules used in the experimental work (Table 1)

Summary

Introduction

Osteoarthritis (OA) is a chronic degenerative joint disease typically affecting the knee, hips, fingers, and/or lower spinal regions [1] and is clinically characterized by gradual development of fluctuating joint pain, swelling, stiffness, and loss of motion [2]. Prevalence increases with age, making OA a leading cause of disability. The prevalence among individuals aged 60 years and older is estimated at 18% of women and 10% of men [3,4]. The options for OA treatment are generally classified as pharmacologic, nonpharmacologic, surgical, complementary and/or alternative [5]. The pharmacological approach is usually based on symptom severity and duration, with the aim of relieving pain and slowing progression of the pathology [7,8,9]. Oral acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay for the treatment of OA. All of these agents have potential gastrointestinal, hepatic, and cardio-renal adverse effects [10] which increase with dosage and duration of treatment

Methods

Results

Discussion

Conclusion