An extract of the medicinal plant Artemisia annua modulates production of inflammatory markers in activated neutrophils

Sheena Hunt,1 Mayumi Yoshida,2 Catherine EJ Davis,2 Nicholas S Greenhill,2 Paul F Davis21Promisia Integrative Ltd, Wellington, New Zealand; 2Trinity Bioactives Ltd, Wellington, New ZealandPurpose: To investigate the ability of a commercial extract from the medicinal plant Artemisia annua to modulate production of the cytokine, tumor necrosis factor-alpha (TNF-α), and the cyclooxygenase (COX) inflammatory marker, prostaglandin E2 (PGE2) in activated neutrophils. Methods: Neutrophils were harvested from rat whole blood and cultured in the presence of plant extract or control samples. Neutrophils, except unactivated control cells, were activated with 10 µg/mL lipopolysaccharide (LPS). The cells were cultured with a range of different concentrations of the A. annua extracts (400–1 µg/mL) and artemisinin (200 and 100 µg/mL) and the supernatants were then tested by enzyme-linked immunosorbent assay (ELISA) for the concentrations of TNF-α and PGE2. Each sample was assayed in triplicate. Positive controls with an inhibitor were assayed in triplicate: chloroquine 2.58 and 5.16 µg/mL for TNF-α, and ibuprofen 400 µg/mL for PGE2. An unsupplemented group was also assessed in triplicate as a baseline control.Results: Neutrophils were stimulated to an inflammatory state by the addition of LPS. A. annua extract significantly inhibited TNF-α production by activated neutrophils in a dose-dependent manner. There was complete inhibition by the A. annua extract at 200, 100, and 50 µg/mL (all P≤0.0003). At A. annua extract concentrations of 25, 10, and 5 µg/mL, TNF-α production was inhibited by 89% (P<0.0001), 54% (P=0.0002), and 38% (P=0.0014), respectively. A. annua 1 µg/mL did not significantly inhibit TNF-α production (8.8%; P>0.05). Concentrations of 400, 200, and 100 µg/mL A. annua extract significantly inhibited PGE2 production by 87% (P=0.0128), 91% (P=0.0017), and 93% (P=0.0114), respectively.Conclusion: An extract of A. annua was shown to be a potent inhibitor of TNF-α and a strong inhibitor of PGE2 production in activated neutrophils at the concentrations tested. Further studies are warranted with this promising plant extract.Keywords: in vitro, TNF-α, COX-2, PGE2, artemisinin, Arthre

Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder

Nathan S Teuscher,1 Akwete Adjei,2 Robert L Findling,3,4 Laurence L Greenhill,5 Robert J Kupper,2 Sharon Wigal6 1PK/PD Associates, Trophy Club, TX, 2Rhodes Pharmaceuticals L.P., Coventry, RI, 3Department of Psychiatric Services and Research, Kennedy Krieger Institute, Baltimore, MD, 4Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, 5Department of Psychiatry, Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY, 6AVIDA Inc., Newport Beach, CA, USA Abstract: A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR) has been evaluated in pharmacokinetic studies in healthy adults and in Phase III efficacy/safety studies in children and adolescents with attention deficit hyperactivity disorder (ADHD). Using available data in healthy adults, a two-input, one-compartment, first-order elimination population pharmacokinetic model was developed using nonlinear mixed-effect modeling. The model was then extended to pediatric subjects, and was found to adequately describe plasma concentration–time data for this population. A pharmacokinetic/pharmacodynamic model was also developed using change from baseline in the ADHD Rating Scale (ADHD-RS)-IV total scores from a pediatric Phase III trial and simulated plasma concentration–time data. During simulations for each MPH-MLR dose level (10–80 mg), increased body weight resulted in decreased maximum concentration. Additionally, as maximum concentration increased, ADHD-RS-IV total score improved (decreased). Knowledge of the relationship between dose, body weight, and clinical response following the administration of MPH-MLR in children and adolescents may be useful for clinicians selecting initial dosing of MPH-MLR. Additional study is needed to confirm these results. Keywords: population pharmacokinetics, Aptensio XR™, MPH-MLR, methylphenidat

A small-scale randomized controlled trial of the revised new forest parenting programme for preschoolers with attention deficit hyperactivity disorder

The revised new forest parenting programme (NFPP) is an 8-week psychological intervention designed to treat ADHD in preschool children by targeting, amongst other things, both underlying impairments in self-regulation and the quality of mother–child interactions. Forty-one children were randomized to either the revised NFPP or treatment as usual conditions. Outcomes were ADHD and ODD symptoms measured using questionnaires and direct observation, mothers’ mental health and the quality of mother–child interactions. Effects of the revised NFPP on ADHD symptoms were large (effect size &gt;1) and significant and effects persisted for 9 weeks post-intervention. Effects on ODD symptoms were less marked. There were no improvements in maternal mental health or parenting behavior during mother–child interaction although there was a drop in mothers’ negative and an increase in their positive comments during a 5-min speech sample. The small-scale trial, although limited in power and generalizability, provides support for the efficacy of the revised NFPP. The findings need to be replicated in a larger more diverse sample. <br/