The study of wound healing activity of Thespesia populnea L. bark, an approach for accelerating healing through nanoparticles and isolation of main active constituents.

The present study provides an evaluation for the wound healing activity of the ethanolic extract of Thespesia populnea L. bark (EBE) and its successive fractions in two doses level (1&2%), designed for determining the most bioactive fraction and the suitable dose. Furthermore, development of the most convenient formulation for these bioactive fractions through either their direct incorporation into hydrogel formulations or incorporation of chitosan-loaded nanoparticles with these bioactive fractions into hydrogel formulations. The highest excision wound healing activity was observed in petroleum ether (Pet-B) followed by ethyl acetate (Etac-B) fractions at the high dose (2%). The most suitable formulation designed for the Etac-B fraction was found to be the chitosan-loaded nanoparticles incorporated in the hydrogel formulation, while the conventional hydrogel formulation was observed to be the highly acceptable formulation for Pet-B fraction. Further phytochemical studies of the bioactive fractions led to the isolation of many compounds of different chemical classes viz; beta-sitosterol and lupeol acetate isolated from the Pet-B, in addition to cyanidin and delphinidin from the Etac-B. Our results revealed that EBE and its bioactive fractions (Pet-B & Etac-B) could be considered as strong wound healers through their anti-oxidant and anti-inflammatory activities, in addition to stimulating collagen synthesis.

Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling.

This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The study evaluated alterations in relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy and phospholipids content, oxidative and nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target of rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood-testis barrier (BTB) remodeling markers, testicular autophagy and apoptotic markers, as well as histopathological alterations in testicular tissues. The results revealed that eugenol treatment demonstrated a significant improvement in sperm quality parameters, with increased sperm cell concentration, progressive motility live sperm, and a reduction in abnormal sperm, compared to the ACR-intoxicated group. Furthermore, eugenol administration increased the levels of seminal plasma amino acids in a dose-dependent manner. In addition, eugenol treatment dose-dependently improved testicular oxidative/nitrosative stress biomarkers by increasing oxidized and reduced glutathione levels and reducing malondialdehyde and nitric oxide contents as compared to ACRgroup. However, eugenol treatment at a high dose restored the expression of AMPK, PI3K, and mTOR genes, to levels comparable to the control group, while significantly increasing p-AKT content compared to the ACRgroup. In conclusion, the obtained findings suggest the potential of eugenol as a therapeutic agent in mitigating ACR-induced detrimental effects on the male reproductive system via amelioration of ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR signaling pathways and BTB remodeling.

Baicalin lipid nanocapsules for treatment of glioma: characterization, mechanistic cytotoxicity, and pharmacokinetic evaluation.

OBJECTIVES: Baicalin is a promising anticancer nutraceutical compound, but its application is hindered by its low water solubility and bioavailability, which can be remedied by its encapsulation in nanoparticles. METHODS: Lipid nanocapsules (LNCs) were developed to enhance baicalin delivery via intravenous and intranasal routes, and potentiate its therapeutic activity in treatment of glioma. RESULTS: LNCs displayed a particle size of 17.76 nm and sustained release of 74.36% after 24 h. The IC50 of baicalin LNCs (13 ± 5 µg/ml) was 60 times lower than free baicalin (780 ± 107 µg/ml) on human glioblastoma multiform cell line U87, with adequate cellular uptake as delineated by confocal laser microscopy. Both baicalin and LNCs induced cell cycle arrest at S and G2/M phases, with significant up-regulation in P21 gene, and decline in Nrf-2, HO-1 and VEGF gene expression. LNCs increased baicalin's bioavailability, either after intravenous (AUC0-24 h 10.94 ± 0.28 vs 3.53 ± 0.09 µg/ml*h), or intranasal administration (AUC0-24 h 6.26 ± 0.11 vs 3.17 ± 0.04 µg/ml*h). They also bypassed the blood brain barrier and achieved significantly higher brain delivery compared to free baicalin (drug targeting efficiency 160.73% vs 52.9%). CONCLUSION: Baicalin LNCs is a promising treatment modality for glioma, when administered through intravenous or intranasal routes.

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats.

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF-MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract's effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF-MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.

Combating hematopoietic and hepatocellular abnormalities resulting from administration of cisplatin: role of liver targeted glycyrrhetinic acid nanoliposomes loaded with amino acids.

The effectiveness of cisplatin in cancer treatment renders its use vital to clinicians. However, the accompanying side effects as cachexia, emesis and liver damage necessitate the use of a dietary supplement which is capable of hindering such undesirable complications. The branched chain amino acids as well as glutamine and arginine have been proven to be effective nutritional co-adjuvant therapeutic agents. Furthermore, new pharmaceutical approaches encompass designing organ-targeted nanoformulations to increase the medicinal efficacy. Therefore, the aim of the present study was to investigate the beneficial effects of liver-targeted amino acids-loaded nanoliposomes in counteracting the adverse hematopoietic and hepatic complications associated with cisplatin. Results revealed the use of the combination of two nanoliposomal formulations (one loading leucine + isolecuine + valine, and the other loading glutamine and arginine) given orally at a dose of 200 mg/kg for twelve days was effective against cisplatin-induced toxicities represented by improvement in the complete blood picture parameters, decrease in the serum hepatic enzymes levels, amelioration of the hepatic oxidative stress and cellular energy imbalance along with reduction in the histopathological abnormalities. It can be concluded that amino acids loaded nanoliposomes could be considered a new strategy in preventing cisplatin's adverse effects.

The herbal preparation STW 5 affects serotonergic pathways in the brain and colon as well as stress parameters in experimental irritable bowel syndrome.

BACKGROUND: Exposure to stress has been related to disturbance in 5-hydroxytryptamine (5-HT) signaling in the brain-gut axis and is considered as a major predisposing factor for the development of irritable bowel syndrome (IBS). The present study aimed to investigate the possible involvement of 5-HT and some other stress-related parameters in the effectiveness of STW 5 against stress-induced IBS. METHODS: Rats were subjected to restraint stress (RS) for 1 h/day for 14 consecutive days to induce IBS-like symptoms and were given STW 5 orally at the same time. At the end of the experiment, blood samples were withdrawn, then animals were euthanized and the brain hippocampi, cerebral cortices, as well as colons were isolated for biochemical and histopathological assessments. RESULTS: RS increased the plasma corticotrophin releasing factor (CRF) with concomitant increase in hippocampal and cortical 5-HT levels, as well as mast cell inflammatory mediators, oxidative stress biomarkers, and histopathological inflammatory changes observed in rat colon. It also decreased the colonic content of 5-HT with consequent decrease in fecal pellet output (FPO). Treatment with STW 5 protected against these changes. CONCLUSION: The protective effect of STW 5 against RS-induced IBS is related to its ability to normalize the induced changes in 5-HT in the brain-gut axis and counteract the stress-induced oxidative stress and inflammation.

Effects of bee venom and dopamine-loaded nanoparticles on reserpine-induced Parkinson's disease rat model.

Parkinson's disease (PD) is a progressive chronic neurodegenerative condition characterized by the loss of dopaminergic neurons within the substantia nigra. Current PD therapeutic strategies are mainly symptomatic and can lead to motor complications overtime. As a result, alternative medicine may provide an effective adjuvant treatment for PD as an addition to or as a replacement of the conventional therapies. The aim of this work was to evaluate the effects of Bee Venom (BV) and dopamine (DA)-loaded nanoparticles in a reserpine-induced animal model of PD. After inducing PD with reserpine injection, different groups of male rats were treated with L-Dopa, BV, DA-nanoparticles. Our findings showed that BV and DA-nanoparticles administration restored monoamines, balanced glutamate/GABA levels, halted DNA fragmentation, decreased pro-inflammatory mediators (IL-1ß and TNF-α), and elevated anti-inflammatory mediators (PON1) and neurotropic factor (BDNF) levels in comparison with conventional therapy of PD. Furthermore, in a reserpine-induced PD rat model, the ameliorative effects of BV were significantly superior to that of DA-nanoparticles. These findings imply that BV and DA-nanoparticles could be useful as adjuvant treatments for PD.

Ginkgo biloba extract (EGb 761) mitigates methotrexate-induced testicular insult in rats: Targeting oxidative stress, energy deficit and spermatogenesis.

Methotrexate (MTX) is commonly used as a therapeutic agent in the treatment of malignancies and autoimmune disorders. Risk of subsequent infertility following MTX administration has been reported as a significant side effect due to testicular toxicity. The aim of the study was to evaluate the modulatory effects of Ginkgo biloba (standardized extract, EGb 761) on MTX-induced testicular oxidative stress, energy deficits and spermatogenic status in rats. All groups received intraperitoneal injection of MTX (0.5 mg/kg) twice weekly for four weeks except the control group that received the corresponding vehicles. Other groups received oral EGb761, at doses 25, 50 or 100 mg/kg/day, for four weeks, concurrently with MTX. Blood and semen sampling followed by testis dissection were performed 24 h after last EGb 761 treatment. Semen was examined for sperm progressive motility, percent of normal spermatozoa and sperm cell concentration as well as seminal plasma essential and non-essential amino acids. Serum LH, FSH and testosterone were detected as well as testicular MDA, GSH, GSSG, TNF-α, IL-1ß, IL-6, NF-κB and the nuclear, cytoplasmic and mRNA expression levels of Nrf-2 besides the testicular cell energy; AMP, ADP and ATP. Histopathological studies of interstitial fibrosis and the severity of germ cell degeneration were also conducted. MTX induced significant decline in sperm quality along with decreased essential and non-essential amino acids in seminal plasma. MTX reduced serum FSH, LH and testosterone as well as testicular ATP, GSH and Nrf2, while increased levels of testicular ADP, AMP, MDA, GSSG and TNF-α. Results were confirmed by prominent interstitial fibrosis and severe germ cell degeneration in MTX group. Concurrent treatment with EGb 761 alleviated MTX-induced testicular insult evidenced by amelioration of oxidative stress biomarkers, energy functions, seminal sperms abnormalities and spermatogenesis status. The present study suggests a beneficial role of EGb 761 in MTX-induced testicular injury and subsequent distortion of spermatogenesis.

Biological and Pharmacological Characterization of Ascorbic Acid and Nicotinamide Chitosan Nanoparticles against Insulin-Resistance-Induced Cognitive Defects: A Comparative Study.

High consumption of industrialized food with high fat content is generally associated with insulin resistance, which in turn causes memory impairment and cognitive decline. Nicotinamide and ascorbic acid are among the promising neuroprotective molecules; however, an appreciable therapeutic activity necessitates the administration of a large dose of either. Therefore, the study aimed to assess if loading them in chitosan nanoparticles in doses 5-10 times lower than the unencapsulated forms would achieve comparable therapeutic results. Animals were fed a high-fat-high-fructose (HFHF) diet for 75 days. The vitamins in their conventional form (100 mg/kg) and the nanoparticles under investigation (10 and 20 mg/kg) were given orally concomitantly with the diet in the last 15 days. The intake of HFHF diet for 75 days led to an insulin-resistant state, with memory impairment, which was verified behaviorally through the object recognition test. This was accompanied by significant reduction in brain insulin-like growth factor 1 (IGF-1), increased acetylcholine esterase activity, increase in the serotonin and dopamine turnover ratio, and increase in oxidative stress and 8-OHdG, indicating cellular DNA fragmentation. Cellular energy was also decreased, and immunohistochemical examination verified the high immunoreactivity in both the cortex and hippocampus of the brain. The administration of nanoparticulated nicotinamide or ascorbic acid with a 10 times lesser dose than the unencapsulated forms managed to reverse all aforementioned harmful effects, with an even lesser immunoreactivity score than the unencapsulated form. Therefore, it can be concluded that nicotinamide or ascorbic acid chitosan nanoparticles can be recommended as daily supplements for neuroprotection in patients suffering from insulin resistance after conduction of clinical investigations.

Ovarian activity and antioxidant indices during estrous cycle of Barki ewes under effect of thyme, celery and salinomycin as feed additives.

This research aimed to examine the effects of thyme, celery and salinomycin on ovarian sex hormones, reproductive traits and antioxidant status during the estrous cycle. Seventy-five mature Barki ewes aged 2-3 years with an average weight of 40 ± 1.5 kg were assigned randomly into five groups (15 head/group). Group 1 was kept as the control; groups 2 and 3 received 20 g/head/day thyme (T) and celery (C) as dried herbs, respectively. Group 4 (T×C) received 10 g thyme + 10 g celery/head/day, and group 5 was treated with salinomycin 1 g/head/day. Blood samples were collected during follicular and luteal phases of the estrous cycle. Thyme and celery and the mixture of T×C increased (P < 0.01) estradiol-17ß (E2) during the follicular phase of the estrous cycle, while only the celery group showed a marked (P < 0.001) increase in progesterone (P4) during the luteal phase compared with the control. Salinomycin supplementation decreased (P < 0.05) E2 concentrations during the follicular and luteal phases of the estrous cycle. Supplementation with thyme and celery enhanced (P < 0.001) antioxidant capacity in the luteal phase compared with the follicular stage. The salinomycin group showed increased (P < 0.01) levels of reduced glutathione (GSH) and decreased malondialdehyde (MDA) levels compared with the control group throughout luteal phase. For the interaction between estrous phases and treatments, thyme, celery, and T×C supplementation revealed an increase (P < 0.05) in superoxide dismutase (SOD), GSH, and glutathione disulfide (GSSG) levels compared with the control group during the follicular and luteal phases. Thyme and celery supplementation improved the number of services per conception and fertilization from 1st and 2nd inseminations, respectively. In conclusion, the applied treatment had significant effects on reproductive performance and antioxidant status in ewes throughout the estrous cycle.

Nicotinamide and ascorbic acid nanoparticles against the hepatic insult induced in rats by high fat high fructose diet: A comparative study.

AIMS: Non-alcoholic fatty liver disease (NAFLD) caused by consumption of high levels of fat and sugars (HFHS) in diet is considered one of the most dangerous medical complications among children and adolescents. Nicotinamide is among the promising candidates in ameliorating HFHS diet-induced NAFLD, but its use is limited by the possibility of prompting hepatotoxicity in high doses. Ascorbic acid is another promising candidate, however its use as a hepatoprotective agent is limited by its chemical instability. Therefore, the aim of the study was to overcome their delivery limitations and enhance their hepatoprotective activity by loading into nanoparticles. KEY FINDINGS: In the present study, upon incorporating nicotinamide or ascorbic acid in chitosan nanoparticles, they ameliorated the insulin-resistant status induced in rats by a high-fat-high-fructose (HFHF) diet. Both formulae decreased serum level of ALT and AST, as well as liver tissue total cholesterol, triglycerides and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. They also decreased oxidative and nitrosative stresses along with a significant increase in the hepatocellular energy. The biochemical findings were further confirmed by histopathological examination. Finally from the obtained data it could be concluded that chitosan nicotinamide nanoparticles at a dose level (10 mg/kg, p.o.) demonstrated beneficial pharmacological effect with safer toxicity profile than chitosan ascorbic acid nanoparticles. SIGNIFICANCE: Nicotinamide chitosan nanoparticles could be recommended as daily supplement in the recovery from NAFLD.

Saussurea lappa root extract ameliorates the hazards effect of thorium induced oxidative stress and neuroendocrine alterations in adult male rats.

The present study was aimed to estimating the effect of Saussurea lappa (costus) root extract on thorium accumulation in different brain regions (cerebral cortex, cerebellum, and hypothalamus) of adult male albino rats and also to evaluate the antioxidant effect and thyroid gland modulation activity of costus following thorium toxicity. Adult male rats were randomly allocated into four groups; control group receiving saline (0.9% NaCl), thorium group receiving an intraperitoneal (i.p.) injection of thorium nitrate (Th; 6.3 mg/kg bwt), costus group receiving an oral administration of costus extract at 200 mg/kg bwt and costus + thorium group receiving costus 1 h before thorium injection. Thorium injection in rats for 28 days resulted in the accumulation of Th maximally in the cerebellum followed by the cerebral cortex and then in the hypothalamus. The accumulation of Th was associated with significant disturbance in sodium and potassium ions. A significant decrease in monoamines was also observed in different brain regions. Furthermore, the results indicated that Th-induced oxidative stress evidenced by increased lipid peroxidation and nitric oxide and decrease the glutathione content. Additionally, Th caused a significant increase in thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels in the serum of rats. However, the pre-administration of costus alleviated all of those disturbances. Our results revealed that costus extract exerted its protective effect mainly through potentiating the antioxidant defense system.

Effects of dietary curcumin and acetylsalicylic acid supplements on performance, muscle amino acid and fatty acid profiles, antioxidant biomarkers and blood chemistry of heat-stressed broiler chickens.

The objective was to investigate the effects of dietary curcumin and acetylsalicylic acid (ASA) on the performance and physiological responses of broiler chickens under chronic thermal stress. One hundred and sixty day-old male chicks (Ross 308) were divided equally into 4 groups (each contained 4 replicates). On the day 22 of age and thereafter, the first group (TN) was raised in a thermoneutral condition (23 ±â€¯1 °C), while the second group (HS) was subjected to 8 h of thermal stress (34 °C) and both groups fed the basal diet with no supplements. The third (CR) and fourth (AS) groups were subjected to the same thermal stress conditions and fed curcumin-supplemented diet (100 mg curcumin kg-1 diet) and ASA-supplemented diet (1 g ASA kg-1 diet), respectively. Dietary treatment had a significant effect on ADFI (P = 0.041), average daily gain (P = 0.013) and final body weight (P = 0.001). The curcumin-supplemented had higher values for these measures compared with other experimental groups (P < 0.05). Also, the dietary curcumin supplement significantly increased the carcass yield as compared to the HS group (P < 0.05). Compared with the HS group, the dietary curcumin and ASA supplements decreased the concentration of malondialdehyde in the breast muscles (P = 0.014). Both dietary supplements exhibited a marked ability to restore the serum TAC, Na and K in heat-stressed broiler chickens. The current study reported a remarkable ability of curcumin supplement to restore the concentrations of polyunsaturated fatty acids (PUFA) in the breast muscles of heat-stressed broilers, including α-linolinec acid and Docosahexaenoic acid (P = 0.009 and 0.001, respectively). It could be concluded that supplemental dietary curcumin or ASA enhanced growth performance and antioxidant biomarkers of heat-stressed broilers. Moreover, curcumin might be an effective dietary supplement to alleviate the adverse effect of chronic thermal stress on carcass yield and meat quality.

Dose-dependent neuroprotective effect of oriental phyto-derived glycyrrhizin on experimental neuroterminal norepinephrine depletion in a rat brain model.

The dose-dependent neuroprotective role of licorice-derived glycyrrhizin during subacute neuroterminal norepinephrine (NE) depletion was studied in rat brain. Experimental design included thirty 5-week-old male rats randomly divided into five groups. Compared to the saline-injected control group, the group receiving daily intraperitoneal injection of fusaric acid (FA; 5 mg/kg/b.w.) for 30 days showed pharmacological depletion of NE. The neuroprotective effects of three successively increasing oral doses of glycyrrhizin were examined in FA-treated rats. Neurochemical parameters and histo-/immunohistopathological changes in the hippocampus were examined. FA generated global hippocampal stress with altered neurobiochemical parameters, accompanied by immune-confirmed inflammatory tissue damage, and noticeable behavioral changes. Although glycyrrhizin after FA-induced intoxication did not correct the recorded drop in the NE level, it decreased the dopamine levels to control levels. Similarly, glycyrrhizin at a high dose restored the serotonin level to its normal value and blocked the FA-induced increase in the level of its metabolite, 5-hydroxyindoleacetic acid. The FA-induced rise in γ-aminobutyric acid (GABA) and histamine was alleviated after administration of a high dose of glycyrrhizin. This was accompanied by improvements in the bioenergetic status and neuronal regenerative capacity through recovery of ATP and brain-derived neurotrophic factor levels to the pre-intoxicated values. High doses of glycyrrhizin also ameliorated the FA-generated behavioral changes and oxidative damage, manifested by the reduction in the expression of cortical pro-apoptotic caspase 3 in the same group. This study suggests that glycyrrhizin can potentially mend most of the previously evoked neuronal damage induced by FA intoxication in the brain of an experimental rat model.

Carcass yields, muscle amino acid and fatty acid profiles, and antioxidant indices of broilers supplemented with synbiotic and/or organic acids.

The objective of the current research was to explore the possible impacts of dietary supplementation with synbiotic and/or organic acids (OA) on the performance traits, carcass yields and muscle amino acid and fatty acid (FA) profiles of broilers. Randomly, a total of 160 day-old chicks (Ross 308) were assigned into four equal groups (40 birds each), with each group subdivided into eight replicates (five birds/pen). The control group (CON) fed the basal diet with no supplements, while diets of the treated groups were supplemented with OA (Sodium butyrate 40%; 1 g/kg), synbiotic (comprised Bacillus subtilis, Saccharomyces cerivisiae, Streptococcus faecium, Mannan-Oligosaccharides and ß-Glucan; 1 g/kg) and equal mix of OA and synbiotic (2 g/kg). Broilers fed the diets supplemented with synbiotic or synbiotic plus OA produced a significantly higher feed utilization efficiency (p = 0.021) and carcass yields (p = 0.038) than the CON and OA-supplemented groups. The group fed the diet supplemented with the synbiotic showed lowered serum cholesterol (p = 0.049), triglycerides (p = 0.001) and very low density lipoprotein (p = 0.032) when compared with the CON group. Regarding the polyunsaturated FA (PUFA) of breast muscles, synbiotic-supplemented birds had significantly lower n-6:n-3 ratio (p = 0.047), however, a greater hypocholesterolaemic to hypercholesterolaemic FA (H/H) ratio was reported when compared with the CON group (p = 0.002). Among the essential amino acids, the contents of leucine and methionine in the breast (p = 0.032 and 0.007 respectively) and thigh (p = 0.023 and 0.003 respectively) muscles were greater in the synbiotic-supplemented birds compared with the CON group. In conclusion, the synbiotic-supplemented diet improved the PUFA:SFA, n-6:n-3 and H/H ratios by altering the FA composition of broiler muscles, which are important with regards to human health.

Amisulpride-CD-Loaded Liposomes: Optimization and In Vivo Evaluation.

Amisulpride (AMS) is an atypical antipsychotic agent used for the treatment of schizophrenia. The effect of different variables, i.e., the type of cyclodextrins (CDs), ratio of drug/CDs, and type of loading on the prepared AMS-CD liposomes (single and double loaded) was studied by applying 23 full factorial design. Double-loaded liposomes are loaded with AMS-hydroxyl propyl-ß-cyclodextrin (HP-ß-CD) in the aqueous phase and free drug in the lipophilic bilayer, while single-loaded liposomes are loaded only with AMS-HP-ß-CD in the aqueous phase. Entrapment efficiency, particle size, polydespersibility, and zeta potential were selected as dependent variables. Design Expert® software was used to obtain an optimized formulation with high entrapment efficiency (64.55 ± 1.27%), average particle size of 40.1 ± 2.77 nm, polydespersibility of 0.44 ± 0.37, and zeta potential of - 48.8 ± 0.28. Optimized formula was evaluated for in vitro release, surface morphology and stability study was also conducted. AMS-HP-ß-CD in double-loaded liposomes exhibited higher drug release than those in the conventional liposomes and in the single-loaded liposomes. The maximum plasma concentration (Cmax) of AMS in optimized AMS-HP-ß-CD double-loaded liposomal formulation increased by 1.55- and 1.29-fold, as compared to the commercial tablets and conventional liposomes, respectively. However, the relative bioavailability of AMS double-loaded liposomes was 1.94- and 1.28-folds of commercial tablet and conventional liposomes, respectively.

Beneficial effects of curcumin nano-emulsion on spermatogenesis and reproductive performance in male rats under protein deficient diet model: enhancement of sperm motility, conservancy of testicular tissue integrity, cell energy and seminal plasma amino acids content.

BACKGROUND: Malnutrition resulting from protein and calorie deficiency continues to be a major concern worldwide especially in developing countries. Specific deficiencies in the protein intake can adversely influence reproductive performance. The present study aimed to evaluate the effects of curcumin and curcumin nano-emulsion on protein deficient diet (PDD)-induced testicular atrophy, troubled spermatogenesis and decreased reproductive performance in male rats. METHODS: Juvenile rats were fed the protein deficient diet (PDD) for 75 days. Starting from day 60 the rats were divided into 4 groups and given the corresponding treatments for the last 15 days orally and daily as follows: 1st group; curcumin group (C) received 50 mg/kg curcumin p.o. 2ndgroup; curcumin nano-form low dose group (NCL) received 2.5 mg/kg nano-curcumin. 3rd group; curcumin nano-form high dose group (NCH) received 5 mg/kg nano-curcumin. 4th group served as malnutrition group (PDD group) receiving the protein deficient diet daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. A normal control group was kept under the same conditions for the whole experiment and received normal diet according to nutrition requirement center daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. RESULTS: PDD induced significant (P < 0.05) reduction in serum testosterone level, sperm motility, testicular GSH, CAT, SOD, testicular cell energy (ATP, ADP and AMP), essential and non-essential amino acids in seminal plasma, an increase in testicular MDA, NOx, GSSG and 8-OHDG. Data was confirmed by histological examination and revealed pathological alteration in the PDD group. Ingestion of curcumin (50 mg/kg) and curcumin nano-emulsion (2.5 and 5 mg/kg) showed significant (P< 0.05) amelioration effects against PDD-induced disrupted reproductive performance as well as biochemical and pathological alterations and the overall results of the nano-emulsion (5 mg/kg) were comparable to curcumin (50 mg/kg). CONCLUSIONS: The present study suggests that administration of curcumin nano-emulsion as a daily supplement would be beneficial in malnutrition- induced troubled male reproductive performance and spermatogenesis cases.