Topical caffeine-loaded nanostructured lipid carriers for enhanced treatment of cellulite: A 32 full factorial design optimization and in vivo evaluation in rats.

The goal of this study was the development and evaluation of semisolid caffeine (CAF) loaded nanostructured lipid carriers (NLCs) for topical treatment of cellulite. CAF-loaded NLC formulations were prepared via high-speed homogenization followed by ultrasonication. A 32 full factorial design was employed for formulation optimization. The total lipid content (%) and the liquid lipid content per total lipids (%) were chosen as factors, whereas particle size (PS), polydispersity index (PDI), zeta potential (|ZP|) and viscosity (VIS) were selected as responses. The design suggested CAF-NLC3 as the optimum formulation consisting of a total lipid content of 15% w/w (palmitic acid and soft paraffin/isopropyl myristate, 7:3 w/w) and a surfactant content of 10% w/w (Tween 80/lecithin, 8:1.2 w/w). CAF-NLC3 revealed PS, PDI, ZP, VIS and CAF content values of 318.8 nm, 0.253, -41.1 mV, 18.0 Pa.s and 97.57%, respectively. It showed a pseudoplastic rheological behavior, acceptable pH value (5.25), good spreadability (1.12 mm2/g) and spherical shape employing transmission electron microscopy. Differential scanning calorimetry and X-ray diffraction demonstrated the amorphization of CAF in CAF-NLC3. CAF-NLC3 remained stable for 3 months at room and refrigeration conditions. A single topical application of CAF-NLC3 on shaved abdominal skins of Wistar rats revealed enhanced skin retention of CAF by 2-fold and 1.4-fold after 4 h when compared with plain CAF gel (CAF-P) and marketed CAF gel (CAF-M), respectively. Furthermore, CAF-NLC3 exhibited a superior anti-cellulite activity in comparison with CAF-P and CAF-M through elevating extracellular matrix components (collagen 1, elastin and hyaluronic acid) and stimulating the brown adipose tissue thermogenesis via up-regulating UCP1 and PPAR-γ expression. In addition, CAF-NLC3 prominently increased lipolysis through HSL activity and decreased pro-inflammatory cytokines such as ICAM-1 and VCAM-1 after 30 days of treatment on a high fat diet-induced cellulite rat model. These findings were further confirmed by histopathological examination supported by morphometric analysis. Therefore, incorporation of CAF in a semisolid NLC formulation would be a promising cosmetic approach for the topical treatment of cellulite.

Effect of Nanosilica and Bentonite as Mycotoxins Adsorbent Agent in Broiler Chickens' Diet on Growth Performance and Hepatic Histopathology.

Mycotoxins are toxic secondary metabolites produced by different strains of fungi, such as aspergillus, fusarium, and penicillium that can contaminate feed ingredients or the entire feed of poultry and animals. Mycotoxins can cause many serious complications to both humans and animals due to carcinogenic, mutagenic, and immunosuppressive disorders. Therefore, the present experiment aims to investigate the effect of broiler chickens' diets supplemented with different levels of nanosilica (NS) as an adsorbent agent of mycotoxins on their growth performance and hepatic histopathology. Detectable levels of toxins were present in the feed before feeding, and all levels of mycotoxins were above the normal limit. A total of 180 one-day-old male Arbor Acres broiler chickens were allocated randomly to six treatment groups with three replicates per group, including ten chickens per replicate. The experiment lasted for five weeks, and dietary treatments included control diet and diets with four levels of nanosilica as 0.05%, 0.10%, 0.15%, and 0.20% as well as 0.50% bentonite (fixfin® Dry) diet. Bodyweight, body weight gain, average daily feed intake, and feed conversion ratio were measured weekly. At the end of the fifth week, six chickens per treatment were sacrificed to investigate the effects of NS and bentonite on carcass characteristics and hepatic histopathology. The results showed that providing broiler chickens' diets with an adsorbent agent, such as NS or bentonite, can reduce the side effects of mycotoxins and enhance their growth performance. The best record was achieved with NS at 0.20%, compared with the control group and other dietary treatment groups. Accordingly, 0.20% of NS could be used in broiler chickens' diets to minimize the harmful effects of mycotoxins.

Protective Role of Casuarinin from Melaleuca leucadendra against Ethanol-Induced Gastric Ulcer in Rats.

Gastric ulcer is a major health problem. Current treatment options of gastric ulcer, including antagonists of histamine H2 receptor and inhibitors of the proton pump, do not cure gastric ulcers, but only provide temporary relief of symptoms and can be associated with severe side effects. The lack of effective and safe medications for this global health problem urges for the discovery of novel classes of compounds with potent activity and an acceptable safety profile. Ethanol-induced ulceration in rats was used to evaluate the gastroprotective activity of casuarinin, an ellagitannin isolated from Melaleuca leucadendra. Casuarinin (25, 50, and 100 mg/kg) reduced the ulcer area by 45, 78, and 99%, respectively, compared with the ulcer group. Casuarinin (100 mg/kg) increased mucin content by 1.8-fold and reduced acidity by 42%. At the same dose, it also increased the levels of reduced glutathione by 194%, catalase by 586%, and prostaglandin E2 to its normal level. In contrast, it attenuated the ethanol-increased levels of malondialdehyde by 56%, TNF-α by 58%, and caspase-3 by 87%. Histological findings demonstrated that casuarinin exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer. Casuarinin suppressed the immunoexpression of nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase to their normal values. It also induced the expression of heat shock protein-70, reaching up to 4.9-fold in comparison with the ulcer group. The potent gastroprotective effect of casuarinin was thus attributed to its anti-inflammatory, antioxidant, and antiapoptotic effects. Our results suggest the potential application of casuarinin as an antiulcer agent from natural sources.

Hepatoprotective activity of praecoxin A isolated from Melaleuca ericifolia against carbon tetrachloride-induced hepatotoxicity in mice. Impact on oxidative stress, inflammation, and apoptosis.

The hepatoprotective activity of praecoxin A, an ellagitannin from Melaleuca ericifolia, was determined against CCl4 -induced toxicity in mice. Praecoxin A was administered (25, 50, and 100 mg/kg) for 5 days followed by CCl4 . Praecoxin A markedly ameliorated the CCl4 -induced increase in AST (by 19, 52, and 56%), ALP (22, 45, and 48%), ALT (11, 47, and 54%), total bilirubin (14, 27, and 28%), and MDA (26, 44, and 51%) at the tested doses, respectively, as compared with CCl4 group. It was evident that praecoxin A significantly (p < 0.001) increased the antioxidant parameters GSH (45, 99, and 137%) and SOD (61, 129, and 159%). Histological findings revealed a marked amelioration of hepatocyte degeneration, necrosis, inflammatory cell infiltration, and hemorrhage in the groups treated with praecoxin A. COX-2 and caspase-3 hepatic expressions were significantly downregulated (p < 0.001) in praecoxin A-treated groups (up to 57, 83, and 93% for COX-2 and by 30, 82, and 99% for caspase-3). These findings suggest that praecoxin A exerts a beneficial effect against oxidative stress by reducing lipid peroxidation, enhancing the antioxidant defense status, and protecting against the histopathological changes induced by CCl4 . This study highlights a promising natural hepatoprotective candidate derived from M. ericifolia that might be an alternative to silymarin.