The effect of transdermally delivered OA (TD OA) alone and in combination with CHQ (CHQ-OA) on hepatic and gastrocnemius glycogen concentrations of <i>P</i>. <i>berghei</i>-infected rats in comparison with control animals (NIC and IC).

<p>The effect of transdermally delivered OA (TD OA) alone and in combination with CHQ (CHQ-OA) on hepatic and gastrocnemius glycogen concentrations of <i>P</i>. <i>berghei</i>-infected rats in comparison with control animals (NIC and IC).</p

The effect of transdermally delivered OA (TD OA) alone and in combination with CHQ (CHQ-OA) on body weight, food and water intake in <i>P</i>. <i>berghei</i>-infected rats in comparison to control animals (NIC and IC).

<p>The effect of transdermally delivered OA (TD OA) alone and in combination with CHQ (CHQ-OA) on body weight, food and water intake in <i>P</i>. <i>berghei</i>-infected rats in comparison to control animals (NIC and IC).</p

Comparison of the effects of oral administration of OA (O OA), transdermal application of OA (TD OA) and CHQ-OA combination (TD CHQ-OA) pectin matrix patches on blood glucose concentrations with those of respective controls and a standard drug CHQ (O CHQ).

<p>Values are presented as means, and vertical bars indicate SEM of means (n = 30 in each treatment group). ^⋆p˂0.05 by comparison with non-infected control animals (NIC), ^♦p˂0.05 by comparison with infected control animals (IC), ^∞p˂0.05 by comparison with CHQ treated animals (O CHQ), ^■p˂0.05 by comparison with oral OA treated animals (O OA), ^#p˂0.05 by comparison with transdermal OA treated animals (TD OA) and ^●p˂0.05 by comparison with CHQ-OA <b>treated</b> animals (TD CHQ-OA).</p

Comparison of the short-term effects of oral administration of OA (O OA), transdermal application of OA (TD OA) and CHQ-OA (TD CHQ-OA) pectin matrix patches with respective controls and a standard drug CHQ (D) on plasma insulin concentrations in <i>P</i>. <i>berghei</i>-infected rats with non-infected (NIC) and infected control (IC) animals.

<p>Values are presented as means, and vertical bars indicate SEM of means (n = 30 in each treatment group).^⋆p˂0.05 by comparison with non-infected control (NIC) animals, ^♦p˂0.05 by comparison with infected control (IC) animals, ^∞p˂0.05 by comparison with CHQ (O CHQ) treated animals.</p

Acute effects of different antimalarial formulations on plasma insulin concentrations in non-infected (A) and <i>P</i>. <i>berghei</i>-infected (B) rats following a 4-hour glucose tolerance test.

<p><b>The blood samples were collected 4 hours after treatment.</b> Values are presented as means, and vertical bars indicate SEM of means (n = 6 in each treatment group).^⋆p˂0.05 by comparison with non-infected control (NIC) animals, ^♦p˂0.05 by comparison with infected control (IC) animals, ^∞p˂0.05 by comparison with CHQ (O CHQ) treated animals.</p

H and E stains illustrating the effects of OA-containing dermal patches on the morphology of the skin.

<p>Picture (6A) represents intact secretory ducts (ISD), uninjured stratum basale (USB) and intact sebaceous glands (ISG) of the non-infected control animals (Mag 7×500 μm). Picture 6B represents intact secretory ducts, uninjured stratum basale and intact sebaceous glands of the <i>P</i>. <i>berghei</i>-infected control (Mag 7×500 μm).Treatment with oral CHQ picture 6C (Mag 7×500 μm) and OA dermal patches picture 6D (Mag 8×500 μm) showed intact secretory ducts, uninjured stratum basale and intact sebaceous glands.</p

Comparisons of OGT responses in non-infected [A] and <i>P</i>. <i>berghei</i>-infected rats [B] to different antimalarial formulations with respective control animals.

<p>Values are presented as means, and vertical bars indicate SEM of means (n = 6 in each treatment group). ^⋆p˂0.05 by comparison with non-infected control animals (NIC), ^♦p˂0.05 by comparison with infected control (IC) animals and ^∞p˂0.05 by comparison with CHQ treated animals (O CHQ).</p

The Effects of Transdermally Delivered Oleanolic Acid on Malaria Parasites and Blood Glucose Homeostasis in <i>P</i>. <i>berghei</i>-Infected Male Sprague-Dawley Rats

<div><p>The present study investigated the effects of transdermally delivered oleanolic acid (OA) monotherapy and in combination with chloroquine (CHQ) on malaria parasites and glucose homeostasis of <i>P</i>. <i>berghei</i>-infected male Sprague-Dawley rats. Oral glucose test (OGT) responses to OA-pectin patch and CHQ-OA combination matrix patch were monitored in non-infected and infected rats. To evaluate the short-term effects of treatment, percentage parasitaemia, blood glucose, glycogen and plasma insulin were monitored in separate groups of animals treated with either OA-patch monotherapy or CHQ-OA combination pectin patch over a 21-days period. Animals treated with drug-free pectin and CHQ acted as untreated and treated positive controls, respectively. Infected control rats exhibited significantly increased parasitaemia which was accompanied by hypoglycaemia. Both OA monotherapy and CHQ-OA combination therapy reduced and cleared the malaria parasites within a period of 4 and 3 days, respectively. Compared to respective controls groups, OGT responses of animals treated with OA monotherapy or CHQ-OA combination therapy exhibited lower blood glucose levels at all time points. A once-off transdermal application of OA-patch or CHQ-OA combination patch significantly improved blood glucose concentrations inducing any changes in insulin concentration. Transdermal OA used as a monotherapy or in combination with CHQ is able to clear and reduce the malaria parasites within a shorter period of time without eliciting any adverse effects on glucose homeostasis of <i>P</i>. <i>berghei</i>-infected rats.</p></div

The effects of oral administration of OA (O OA), transdermal application of OA (TD OA) and CHQ-OA (TD CHQ-OA) pectin matrix patches on percentage parasitaemia in <i>P</i>. <i>berghei</i>-infected rats.

<p>Values are presented as means, and vertical bars indicate SEM of means (day 0, n = 30; day 7, n = 24; day 9, n = 18; day 12, n = 12; day 21, n = 6). ^⋆p˂0.05 by comparison with control animals.^∞p˂0.05 by comparison with oral CHQ treated animals.</p