Clinical trial for evaluating the effectiveness and tolerability of topical Sphaeralcea angustifolia treatment in hand osteoarthritis

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Abstract

Ethnopharmacological relevance

Sphaeralcea angustifolia Cavanilles & Don (Malvaceae), known in Mexico as “Vara de San José”, is used in Mexican Traditional Medicine as an anti-inflammatory and, more specifically, for treating rheumatism. Anti-inflammatory properties have been demonstrated in different pharmacological models.

Aim of the study

The therapeutic effectiveness and tolerability of the topical administration of a gel elaborated with a standardized Sphaeralcea angustifolia extract applied to patients with Hand osteoarthritis (HOA) was evaluated.

Materials and methods

A pharmaceutical formulation in a gel presentation that contained a standardized extract (hydroxycoumarin content) of Sphaeralcea angustifolia was elaborated and later evaluated in a double-blind, randomized study controlled with a similar formulation containing 2% diclofenac. Treatments were administered topically for 4 weeks on the affected hand(s). Clinical evolution was followed weekly by means of the Algofunctional Index (AFI) and the Visual Analog Scale (VAS).

Results and discussion

A total of 130 participants were included in the study. Among these, 113 were considered in the analysis (55 in the experimental group and 58 in the control group). In both groups, important improvement in the patients' symptomatology was noted. Therapeutic effectiveness was 89% and 91.3% in the two groups, respectively, without a statistically significant difference between the groups. None of the treatments presented any adverse effects.

Conclusion

The 4-week topical administration of a gel formulation elaborated with a 1% standardized extract of Sphaeralcea angustifolia showed therapeutic effectiveness and tolerability when administered to patients with HOA, without exhibiting significant differences when compared with the effect observed in patients treated with 2% diclofenac.

Graphical abstract

Graph that shows the effect produced by topical administration of a phytopharmaceutical elaborated with the standardized extract of Sphaeralcea angustifolia (Exp) or by the treatment containing 2% diclofenac (Control), during the 4 treatment weeks. Evaluation was effected with the Algofunctional Index (AFI) of the hand, in which a high value signifies more difficulty and a low value signifies less difficulty in performing daily manual tasks.

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Introduction

Osteoarthritis (OA) is a chronic disease of the joints and is the most frequent form of arthritis (Martín, 1990). Its main clinical demonstrations are pain, stiffness, cracking around the joint, deformation, and limitation of movement (Klippel, 1997, Blanco et al., 2001). The main factors that predispose for this disease are age, type of work, gender, and race, in addition to multiple other factors such trauma, obesity, genetic mutations, familial antecedents, and some metabolic alterations (Hochberg, 1991, Allen et al., 2009, Liberopoulos et al., 2009, Scher et al., 2009, Velasco et al., 2010). OA is a very frequently occurring disease that mainly affects women and that produces pain and movement limitation that in turn affects the productive life of patients. In Mexico, during the decade of 1990, OA was the first cause of Years lived with a disability (YLD) and the ninth cause of Years of potential life lost (YPLL) (Lozano et al., 1996).

In order to treat OA and in addition to pharmaceutical drugs, there are different alternative therapies, such as herbal treatments (Chrubasik et al., 2007). Sphaeralcea angustifolia Cavanilles & Don (Malvaceae) is popularly known in Mexico as “hierba del negro”, “hierba de vara de San José”, or “hierba del golpe” (Aguilar et al., 1994). This plant species has been widely used in Mexican Traditional Medicine for the treatment of different diseases related with an inflammatory process, such as tonsillitis, bronchitis, conjunctivitis, gastritis, and enteritis, as well as for the treatment of contusions and hemorrhoids (Díaz, 1976). Aerial parts of this plant, macerated in alcohol, are employed in Mexico for the treatment of rheumatism (Andrade-Cetto, 2009). The product is topically administered for treating arthritis. This plant has been evaluated in different in vivo models, which have evidenced anti-inflammatory activity produced by the dichloromethane extract of the species. This extract has been effective when administered systemically or topically in the experimental model of arthritis induced in rats with 12-ortho-Tetradecanoylphorbol-13-acetate (TPA). Other in vitro experimental procedures have shown that this same extract has the capacity to inhibit the cytokines that comprise a main characteristic of response in chronic inflammation and that contribute to establishing a possible mechanism of action based on the type of genetic expression regulation (Meckes et al., 2004, Juárez, 2008). From the active fraction, the following different compounds have been identified: scopoletin; stigmasterol; β sitosterol; a mixture of α- and β-amyrin, and trans-cinnamic acid (García et al., 2012).

The objective of this study was to produce a phytopharmaceutical (in a gel presentation) containing the standardized extract of Sphaeralcea angustifolia in its hydroxycoumarin (scopoletin and tomentin) contents and to evaluate its therapeutic effectiveness and tolerability when administered topically in patients with HOA.

Section snippets

Plant material

The plant material of Sphaeralcea angustifolia Cavanilles & Don (Malvaceae) was collected in Hidalgo State, Mexico. Herbarium samples were prepared for its identification and protection; this was carried out at the Mexican Institute of Social Security's Herbarium (Mexico City) by Herbarium Director Abigail Aguilar-Contreras, M.Sc. The registration number for reference of this sample was IMSSM-15544.

Extract preparation

The aerial parts of the plant were selected and submitted to a drying procedure at room

Baseline characteristics of the population under study

A total of 130 patients were included in the study, 65 in each group. In the first part of the analysis, familial and personal records were taken, as well as those related with the present disease and physical exploration. All of the patients were included in the analysis. In the second part of the analysis, values obtained from the weekly clinical evaluations were considered, and only 55 (84.6%) and 58 (89.2%) patients from the experimental and control groups, respectively, were included.

Discussion

Osteoarthritis (OA) is recognized as the main cause of muscular–skeletal pain and disability (Therkleson, 2010). Hand osteoarthritis (HOA) is a chronic degenerative disorder that affects adults with a prevalence of 13% in males and 26% in females (Widrig et al., 2007). In this study, the participation of females was considerably larger than that of males, probably due to greater willingness to participate in the study. This is a progressive disease that gradually destroys cartilage on both

Conclusion

Considering these aspects of the study, it is possible to conclude that the topical administration, during 4 weeks, of a gel formulation elaborated with the standardized extract of Sphaeralcea angustifolia at 1% showed therapeutic effectiveness and tolerability in patients with HOA, without presenting significant differences compared with the effect on patients treated, in the same way and during the same amount of time, with 2% diclofenac.

Conflicts of interest

No conflict of interest was declared by the collaborators who participated in the study.

Acknowledgments

This study was financially supported by the Health Research Fund (FIS/IMSS/PROT/G10/822 and CONACyT Salud 2013-CO1-201267). We thank Abigail Aguilar-Contreras, M.Sc., for her support in identifying the plant species, and Juan Pablo Tortoriello for his support in the translation of the article.

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