Contribution to the Valorization of Plants Used in the Management of Rheumatic Diseases in Burkina Faso

Joint pain is a real public health problem. According to recent studies, it is increasingly common in sub-Saharan Africa and represents a cause of greater loss of working days than accidents, heart disease and infections. The aim of this study was to study the pharmacochemical and therapeutic evidence of ten (10) plants used in the management of joint pain by traditional health practitioners in Ouagadougou. We conducted a meta-analysis of the data from December 2018 to September 2019. The anti-inflammatory activity of the ten (10) plants retained the maximum consensus internationally. Trichilia emetica Vahl (35.25%), Guiera senegalensis J.F.G.mel. (31%), Calotropis procera (Ait) Ait.F. (28.29%) and Crescientia cujete L. (25.12%) had more than 25% internationally reliability for their effects on joint pain. The structural analogy between conventional drugs and the molecules found in these plants has been confirmed. Additional studies should be carried out in order to improve and secure the use of these plants, which represent a prominent option in the therapeutic offer. identified in Trichilia emetica Vahl, Guiera senegalensis J.F.G.mel., Calotropis procera (Ait) Ait.F. These observations strengthen scientific basis for the use of Trichilia emetica Vahl, Guiera senegalensis J.F.G.mel., Calotropis procera (Ait) Ait.F. and Crescientia cujete L. in inflammatory joint pain treatment. The subsequent evaluation of therapeutic equivalences will allow the devel-opment of plant-based phytomedicines, standardized in therapeutic equivalent of modern treatments per gram of dry plant material. Evaluation of QSAR of plant compounds as indolic alkaloids and modified triterpenic compounds with potent anti-inflammatory properties could give models for drug design and dis-covery in the area of new therapies development.


Introduction
Rheumatism is a public health problem in developed countries. Sub-Saharan African countries are not concerned with because of priority diseases such as malaria, cardiovascular diseases and human immunodeficiency virus (HIV) infection. Over the last ten years, many studies have reversed this perception in low-income countries weakly affected by rheumatic diseases like rheumatoid arthritis (RA) [1]. For example, rheumatoid arthritis, which is chronic inflammatory and autoimmune rheumatism, had a world prevalence of 0.4% -1% in 2015. In Burkina Faso, in-hospital frequency of 2.18% was reported by a study covering the period from 2006 to 2011 [2].
Rheumatism is a common chronic inflammatory disease, characterized by dysregulated inflammatory process in joint synovium that leads to the destruction of both cartilaginous and bones, resulting in pain, disability and destruction of articular structures. Complex autoimmune and inflammatory processes induce synovitis, swelling, and joint damage, after activation of components in both innate and adaptive immune systems. Rheumatism causes pain, weariness, and disability associated with a significant reduction in health-related, well-being and quality of life [3].
In community and economic fields, rheumatic diseases cause an invaluable loss of working time, greater than accidents, cardiovascular diseases and infections. The problem of Rheumatic-related disability is even pronounced in manual workers where entire musculoskeletal system is most solicited [4]. Repetition of painful crises and rheumatic disability compel patients to resort to both conventional, alternative or traditional medicine therapeutic care. Therefore, more than 80% of the West African population resort to traditional medicine for treatment [5]. This therapeutic care is highly dependent on medicinal plants use and associated local knowledge [6] [7]. Cultural beliefs have a deep impact on choice of traditional medicine care by populations compared to economic reasons. Supply of health care and access to medicines is very weak or even non-existent and so expensive for African population. Moreover, despite the availability of generic drugs, many innovative treatments such as targeted therapy with monoclonal antibodies, remain inaccessible to low-income populations. Prices of conventional medicines range from two (2) dollars (antiinflammatory drugs) to 100 dollars (targeted therapy) compared to traditional rarely exceed 1 dollar. Then, traditional medicine becomes a good alternative for health care coverage, especially in case of chronic pathology [5]. Hence, promoting traditional medicines and practices is encouraged by WHO and is included in public health policies in low-income countries. In Burkina Faso, out of 2067 species are listed and half have been registered with traditional uses including rheumatic diseases [2]. In a previous ethnobotanical survey, we reported that 73 species from 70 genera and 41 families are used by traditional health practitioners for rheumatism treatment in Ouagadougou, the political capital of Burkina Faso. The ten (10) most cited plants were selected for this study purpose We then carried out a meta-analysis of the available scientific data pharmacologic properties of these plants in inflammatory joint pain relief. We also analyzed structural analogies between modern therapies compounds and plant metabolites to suggest qualitative structure-activity relation in pharmacological potential of these ten plants.

Determination of Consensus Factors (FIC) and Fidelity Levels (FL) of Studied Plants
Determination of the informant consensus factor (FIC) and the fidelity level for identified plants was carried out online on 18 December 2018 according to method described by Hassan et al. [8]. We conducted a meta-analysis on the pharmacological properties of the 10 selected plants from December 2018 to September 2019. Table 1 shows the different plant parts used in the treatment of rheumatic diseases, according to Youl et al. [2]. Research on scientific papers (26,595 articles) on plants has identified information on their chemical composition and pharmacological effects on rheumatic diseases (including joint pain).

Factor of Informant Consensus
The Informant Consensus Factor (FIC) represents independent variables that contribute to the agreement and consent in international scientific opinion. It was determined as previously described by Hassan et al. [8].
with: N ur , scientific articles related to the therapeutic use of the plant; N t , plant species and for calculations, N t = 10.

Fidelity Level
Fidelity Level (FL) represents the accuracy of the claimed medicinal use [9].
( ) with: X 1 , scientific articles combining plant and joint pain; X 2 , scientific articles combining plant and anti-inflammatory; X 3 , scientific articles combining plant and antirheumatic; Y, number of all citations for the name of the plant only.
Data was analyzed on Microsoft Excel 2013, and thresholds for data analysis have been set at 25% which represent the strength of fidelity showing that this indication is well recognized for this plant.

Study of Structural Analogies between Selected Plant Secondary Metabolites and Antirheumatics
Drugs used as antirheumatics for structural analogies study, include nonsteroid-

Determination of the Informant Consensus Factors and Fidelity Levels of Identified Plants
Review on scientific articles related to pharmacological activities of selected plants is presented in Table 2.
Zizyphus mauritiana Lam. was subject to the largest number of scientific publications (5610) while Trichilia emetica Vahl had 644 publications. Anti-inflammatory use of these ten (10)   Estimation of fidelity level of use on inflammatory joint pain management showed 4 plants with more than 25% fidelity of claimed on inflammatory joint pain such as Trichilia emetica Vahl (35.25%), Guiera senegalensis J.F.G.mel. (31%), Calotropis procera (Ait) Ait.F. (28.29%) and Crescientia cujete L. (25.12%). Indeed, Trichilia emetica Vahl root powder mixed with potassium hydroxide and water traditionally cures inflammation [5]. Guiera senegalensis leaves extracts showed an analgesic effect and are widely used against rheumatism [7]. Calotropis species are used for the treatment of pain and rheumatism, like roots used against rheumatism, and latex and leaves used in the treatment of joint pain. So, several studies provide evidence of Calotropis species analgesic, anti-inflammatory and anti-nociceptive properties [10]. Crescientia cujete L. extracts exhibit antiinflammatory activities [11] [12].

Study of Structural Analogies between Selected Plants Secondary Metabolites and Antirheumatics
Structural analogies between secondary metabolites found in selected plants and antirheumatic drugs are presented in Table 3 and Table 4    Colchicine Antigout H

Basic Chemical Skeletons Corresponding to Phenolic Compounds
Analgesics and anti-inflammatories drugs used in the treatment of rheumatic pathologies presented a basic chemical skeleton like C 6 -C 1 , C 6 -C 2 and C 6 -C 3 type (Table 3), close to those of plant phenolic compounds [13]. Study of chemical compounds found in plants with the highest level of agreement for inflammatory joint pain care also indicates the presence of compounds showing similar basic skeletons C 6 -C 1 and C 6 -C 3 type.

Basic Chemical Skeletons Corresponding to Terpenic Compounds
Drugs used in inflammatory joint pain care present basic chemical skeletons close to steroid-like triterpene derivatives as corticosteroids and their derivatives ( Table 4). Scientific publications indicate that many plant-derived triterpenes have anti-inflammatory properties [23].

Basic Chemical Skeletons Corresponding to Nitrogen Compounds
Observations of chemical structures indicated that morphine and piroxicam have basic chemical skeletons of C 6 -C 2 -N type while colchicine would be of C 6 -C 3 -N type (Table 3) close to phenylalanine-derived compounds. Many alkaloids, especially the iso-quinoline alkaloids, exhibiting the same basic skeletons, are known to have anti-inflammatory and analgesic properties [27].
Study of chemical compounds found in plants with the highest level of agreement for inflammatory joint pain care also indicates the presence of nitrogen  have not been identified in Guiera senegalensis J.F.G.mel. [18], Calotropis procera (Ait) Ait.F. [10], and Crescientia cujete L. [11]. Nevertheless, we noted in Guiera senegalensis J. F. G. mel the presence of indolic alkaloids β-carboline type as harmalane, harmane and tetrahydroharmane ( Figure 2) [28]. These compounds demonstrated anti-inflammatory activities by suppressing nitric oxide production and secretion of pro-inflammatory cytokines [29]. Similarly, nitrogen compounds like choline has been identified in the latex of the leaves of Calotropis procera (Ait) Ait.F. Choline is a quaternary ammonium-like proto-alkaloid [30] that showed anti-inflammatory effects. We could not identify structural analogies between these nitrogen molecules, which potent anti-inflammatory properties have been already demonstrated and modern antirheumatics.

Conclusions
Determination of informing consensus factor and the fidelity level attest to the efficiency of selected plants for traditional care of joining pain and give evidence for a scientifically recognized worldwide. Study of structural analogies between plants compounds used in the treatment of inflammatory rheumatic diseases and modern drugs' basic chemical skeleton indicates many similarities. Phenolic compounds C 6 -C 1 , C 6 -C 3 type, similar to basic skeletons of anti-inflammatory and analgesic are found in selected plants. Then, steroid-like terpenic compounds with basic chemical skeleton close to corticosteroids have been identified in Trichilia emetica Vahl, Guiera senegalensis J.F.G.mel., Calotropis procera (Ait) Ait.F. These observations strengthen scientific basis for the use of Trichilia emetica Vahl, Guiera senegalensis J.F.G.mel., Calotropis procera (Ait) Ait.F. and Crescientia cujete L. in inflammatory joint pain treatment.
The subsequent evaluation of therapeutic equivalences will allow the development of plant-based phytomedicines, standardized in therapeutic equivalent of modern treatments per gram of dry plant material. Evaluation of QSAR of plant compounds as indolic alkaloids and modified triterpenic compounds with potent anti-inflammatory properties could give models for drug design and discovery in the area of new therapies development.