Caryocar coriaceum Wittm. fruit extracts as Leishmania inhibitors: in-vitro and in-silico approaches.

Leishmaniasis is a group of neglected diseases caused by parasites of the Leishmania genus. The treatment of Leishmaniasis represents a great challenge, because the available drugs present high toxicity and none of them is fully effective. Caryocar is a botanical genus rich in phenolic compounds, which leaves extracts have already been described by its antileishmanial action. Thus, we investigated the effect of pulp and peel extracts of the Caryocar coriaceum fruit on promastigote and amastigote forms of Leishmania amazonensis. Both extracts had antipromastigote effect after 24, 48, and 72 h, and this effect was by apoptosis-like process induction, with reactive oxygen species (ROS) production, damage to the mitochondria and plasma membrane, and phosphatidylserine exposure. Knowing that the fruit extracts did not alter the viability of macrophages, we observed that the treatment reduced the infection of these cells. Thereafter, in the in vitro infection context, the extracts showed antioxidant proprieties, by reducing NO, ROS, and MDA levels. Besides, both peel and pulp extracts up-regulated Nrf2/HO-1/Ferritin expression and increase the total iron-bound in infected macrophages, which culminates in a depletion of available iron for L. amazonensis replication. In silico, the molecular modeling experiments showed that the three flavonoids presented in the C. coriaceum extracts can act as synergistic inhibitors of Leishmania proteins, and compete for the active site. Also, there is a preference for rutin at the active site due to its greater interaction binding strength.Communicated by Ramaswamy H. Sarma.

Phosphatidylserine reverses reserpine-induced amnesia.

The effects of phosphatidylserine (PS) were studied in rats treated with reserpine (1 mg/kg) immediately after training in the passive avoidance task. In experiment I, phosphatidylserine (25 mg/kg) was administered 30 min before or immediately after training. Acute pre- or post-treatment with phosphatidylserine was effective in reversing the amnestic effect of reserpine in test trials performed 24 h and 1 week after training. Experiment II was performed to determine if the long-term pretreatment with phosphatidylserine (25 mg/kg) for 7 days is able to protect the rats against the amnestic effects of reserpine in this task. The data show that phosphatidylserine reverses the impairment induced by reserpine in trials performed 24 h and 1 week after training. These results indicate that the memory deficits associated with catecholamine depletion caused by reserpine can be attenuated by acute pre- or post-training or by long-term pretreatment with this phospholipid.

For cognitive enhancement provider system (FORCEPS) preventive geriatrics: our cardinal challenge

Recent revelations restoring telomeres and using citicoline to rejuvenate cerebral function post-stroke make it highly probable that human lifespan (with acceptable cerebration) can be extended to a theoretical limit of 120-140 years. However, millions of people are already taking anti-aging products of uncertain quality and quantity without any objective measurements of their effectiveness, such as on short-term memory loss. No drug company will undertake these very expensive studies on nonpatentable products. FORCEPS was designed to evaluate anti-aging and SMART drugs, herbs and supplements through a network of practitioners in preventive geriatrics, communicating through weekly telephone conference and a FORCEPS newsletter. Currently, the focus is on acetyl-carnitine coenzyme 0-10, deprenyl (selegiline), gingko bilboa, phosphatidyl serine and piracetam. For prescription medicine such as deprenyl and piracetam. FORCEPS maintain alist od compounding mail-order pharmacies to facilitate in-office physician dispensing for non-FDA approved uses. The non-prescription items are available through the FORCEPS multi-level marketing (MLM) network, whereby the customers (including providers) can purchase the products wholesale and also derive income by sponsoring new customers who maintain monthly product purchase levels for self use and resale. The major incentives for customers to purchase through FORCEPS would be the motoring and advice in anti-ageing therapy, and the potential for income through sponsoring new participants in the MLM network. By providing products of pharmaceutical-grade quality and standardized protocols to experienced geriatricians, FORCEPS will coordinate and communicate the evaluation of these products among thousands of customers in the only way possible - applied real life research analysis to determine what really works.(AU)