<p>Inhibition of <em>Trypanosoma evansi</em> Protein-Tyrosine Phosphatase by Myristic Acid Analogues Isolated from <em>Khaya senegalensis</em> and Tamarindus <em>indica</em></p>

Abstract

BackgroundTrypanosome infections still pose severe health and economic consequences, especially in the endemic regions of Sub-Saharan Africa. Trypanosome differentiation to the procyclic forms which lack the immune evasion mechanisms for survival in the bloodstream is prevented by tyrosine dephosphorylation which is catalyzed by protein-tyrosine phosphatase; thereby promoting survival of the parasites in the host. Inhibition of Protein-tyrosine phosphatase is a strategic therapeutic target that could attenuate trypanosomiasis. This study investigated the in vitro inhibitory effect of stem bark extracts of Khaya senegalensis and Tamarindus indica on the enzymatic activity of protein-tyrosine phosphatase.MethodsAll determinations were carried out following standard procedures for analytical experiments. The analogues of myristic acid that inhibited the enzymatic activity of protein-tyrosine phosphatase were isolated by bioassay-guided fractionation of stem bark extracts of Khaya senegalensis and Tamarindus indica.ResultsAnalogues of myristic acid proved to be potent inhibitors of protein-tyrosine phosphatase. Double reciprocal (Lineweaver–Burk) plots of the initial velocity data indicated non-competitive inhibition with Ki of 0.67 mg/mL for Khaya senegalensis and 2.17 mg/mL for Tamarindus indica. The kinetic parameters for the cleavage of para-nitrophenylphosphate by the enzyme showed a KM of 3.44 mM and Vmax of 0.19 µmol/min. Sodium orthovanadate, the enzymes’ specific inhibitor, inhibited the enzyme competitively with Ki of 0.20 mg/mL. Gas chromatography-mass spectrometry analysis of the stem bark bioactive fractions of Khaya senegalensis and Tamarindus indica revealed the presence of myristic acid analogues.ConclusionAnalogues of myristic acid are potent inhibitors of protein-tyrosine phosphatase that could be developed as trypanocide to inhibit the enzymatic activity of protein-tyrosine phosphatase in order to prevent transmission of trypanosomes.

Associations of serum long-chain fatty acids with multiple organ involvement in patients with sarcoidosis

“…OR, odds ratio; CI, confidence interval; BMI, body mass index; ACE, angiotensinconverting enzyme; FVC, forced vital capacity; FEV 1 , forced expiratory volume in 1 s; SFAs, saturated fatty acids; PUFAs, polyunsaturated fatty acids; MUFAs, monounsaturated fatty acids a Per 1-year increase The potential mechanisms for the effects of SFAs on immune systems were reported to include protection from pathogenic microorganisms possibly by activating the Toll-like receptor 4 signaling pathway [36]. Therefore, lower levels of SFAs were associated with poor outcomes in infectious diseases, while supplementation of SFAs improved these outcomes [37,38,39,40]. However, the underlying mechanisms for the association of decreased levels of SFAs with multiple organ involvement in patients with sarcoidosis remain unknown.…”

Molecular and phylogenetic analysis of a type K1 strain Trypanosoma evansi isolate from Nigerian cattle: An evaluation of the therapeutic effects of compounds from Brassica oleracea on the histopathology of infected wister rats

“…Surra is caused by T. evansi in domestic and wild animal reservoirs, as well as in humans [ [1] , [2] , [3] , [4] ]. The disease is still endemic in Sub-Saharan Africa [ [5] , [6] , [7] , [8] , [9] , [10] ], and it has historically prevented the development of vast swaths of African land into highly productive agricultural areas [ 9 ]. The disease has a significant socioeconomic impact and reduces animal productivity globally [ 11 ].…”

“…The disease has a significant socioeconomic impact and reduces animal productivity globally [ 11 ]. T. evansi has the broadest range of hosts and geographical distribution of any pathogenic trypanosoma species, infecting a wide variety of mammalian hosts and other animals [ 11 , 12 ], and causing wasting disease ( Surra ) in livestock [ 10 , 12 ]. T. evansi was the first pathogenic mammalian trypanosome discovered in the blood of Indian equines and dromedaries in 1880 by Dr. Griffith Evans [ 11 , 13 ].…”

“…Anemia and infertility are common clinical manifestations of T. evansi infection. It is spread mechanically by hematophagous flies of the genera Stomoxys and Tabanus [ 10 , 11 ].…”

“…As a result, control is still based on a combination of active case diagnosis and treatment, as well as vector control [ 20 , 21 ]. In the absence of effective vaccination, due to surface membrane modification [ 10 ], control of trypanosomiasis could be achieved primarily through chemoprophylactic or chemotherapeutic agents [ 22 ], so investigating other options became important.…”