Bioguidage search of active compounds from Waltheria indica L. (Malvaceae) used for asthma and inflammation treatment in Burkina Faso

Waltheria indica is used in traditional pharmacopeia in Burkina Faso for the treatment of asthma and conditions of inflammation. To evaluate its pharmacological properties and isolate the active compounds, a study through a bioguided phytochemical approach was conducted. This search was guided by a two‐level investigation. First, we evaluated the impact of various fractions on the activity of enzymes involved in smooth muscle contraction (PDE4A1α) and inflammatory processes (PLA₂, 5‐LOX). Second, we investigated the inhibitory effect of fractions on isolated rat trachea. The initial hydroalcoholic extract from roots of W. indica (HA), n‐hexane fraction (F₁), dichloromethane fraction (F₂), ethyl acetate fraction (F₃), residuary fraction (F₄) reduced enzyme activity of PDE4A1α (inhibition of 22–42% at 50 μg/mL), 5‐LOX (60–80% at 10 μg/mL), and PLA₂ (42–94% at 100 μg/mL). On isolated rat trachea, only HA, F₃, and fractions obtained from F₃ by chromatography on silica gel column, using dichloromethane/methanol, dose dependently inhibited contraction induced by acetylcholine. IC₅₀ was 1051 μg/mL for HA and comprised between 181 and 477 μg/mL for F₃ and its fractions. The most active fractions were purified and led to the identification of (‐)‐epicatechin. (‐)‐epicatechin from W. indica dose dependently inhibited PLA₂ (IC₅₀ = 154.7 μm ) and 5‐LOX (IC₅₀ = 15.8 μm ). In conclusion, both inhibition of PDE4A1α, 5‐LOX, and PLA₂ activities and rat trachea relaxation by W. indica validate its use in traditional management of asthma and other conditions of inflammation. These effects should be, at least in part, attributed to the presence of (‐)‐epicatechin in roots of W. indica.     

Tryptophan 650 of human granulocyte colony-stimulating factor (G-CSF) receptor, implicated in the activation of JAK2, is also required for G- CSF-mediated activation of signaling complexes of the p21ras route

Granulocyte colony-stimulating factor (G-CSF) induces rapid phosphorylation of JAK kinases as well as activation of the p21ras route through interaction with its specific receptor (G-CSF-R). The cytoplasmic membrane-proximal region of G-CSF-R (amino acids 631 to 684) is necessary for proliferation induction and activation of JAK2. In contrast, activation of Shc and Syp, signaling molecules implicated in the p21ras signaling route, depends on the phosphorylation of tyrosine residues located in the membrane-distal region (amino acids 685 to 813) of G-CSF-R. We investigated whether G-CSF-induced activation of signaling complexes of the p21ras route depends on the function of the membrane-proximal cytoplasmic region of G-CSF-R. A G- CSF-R mutant was constructed in which tryptophan 650 was replaced by arginine and expressed in BAF3 cells (BAF/W650R). In contrast to BAF3 cell transfectants expressing wild-type G-CSF-R, BAF/W650-R cells did not proliferate and did not show activation of JAK2, STAT1, or STAT3 in response to G-CSF. Immunoprecipitations with anti-Shc and anti-Grb2 antisera showed that mutant W650R also failed to activate Syp and Shc. These data indicate that the membrane-proximal cytoplasmic domain of G- CSF-R is not only crucial for proliferative signaling and activation of JAK2 and STATs, but is also required for activation of the p21ras route, which occurs via the membrane-distal region of G-CSF-R.     

Anatomy of the ilium for bone marrow aspiration: map of sectors and implication for safe trocar placement

Purpose

The bony anatomy of the human ilium has been well described from a qualitative perspective; however, there are little quantitative data to help the surgeon to perform bone marrow aspiration from the iliac crest in the thickest part of the ilium. The minimum thickness of the spongiousus bone in an iliac wing (transverse thickness between the two tables) is an important factor in ensuring the safe placement of a trocar between the two tables of the iliac wing. For example, with an 8-gauge (3.26 mm) trocar, one can consider that if the transverse thickness of the spongiousus bone of the iliac wing is <3 mm, it will be difficult to insert the trocar safely between the two tables.

Methods

For this study, we measured spongiousus bone thickness on 48 iliac wings to map the ilium in six sectors, which were defined by drawing lines from equidistant points spaced along the rim of the iliac crest to the centre of the hip. These sectors can be transposed in the same manner to any patient. To evaluate the risks to reach vascular or neurologic structures, 410 trocars were introduced in the different sectors of 20 iliac bones of ten cadavers.

Results

A map was constructed indicating the thickness of the spongiousus bone in each sector. The thickness data was used to create a map that identifies the sites where bone marrow can be obtained with a trocar of 3-mm diameter according to the thickness of the spongiousus bone. Sectors 2, 3 and 6 appear to be more favourable for accommodating a 3-mm diameter trocar. Sectors 1, 4 and 5 comprise the areas with the thinnest parts of the iliac crest, with some areas being thinner than the trocar diameter. The sector system reliably predicted safe and unsafe areas for trocar placement. In cadavers, dissection demonstrated nine vascular or neurologic lesions created when trocars were introduced into sectors 1, 5 and 6.

Conclusion

Using the sector system, trocars can be directed away from neural and vascular structures and towards zones that are likely to contain larger bone marrow stock.