Rosmarinus officinalis L. extract and some of its active ingredients as potential emulsion stabilizers: a new approach to the formation of multiple (W/O/W) emulsion

Nowadays, novel topical formulations loaded with natural functional actives are under intense investigations. Therefore, the aim of our study was to evaluate how the rosemary extract and some of its active ingredients [rosmarinic acid (RA), ursolic acid (UA) and oleanolic acid (OA)] affect technological characteristics of multiple emulsion. Formulation has been prepared by adding investigated solutions (10%) in water/oil/water (W/O/W) multiple emulsion consisting of different lipophilic phases: olive oil and liquid paraffin, with 0.5% emulsifying agent (complex of sodium polyacrylate and polysorbate 20) under constant stirring with mechanical stirrer at room temperature. The emulsion parameters were evaluated using centrifugation test, freeze–thaw cycle test, microscopical and texture analyses. Rosemary's triterpenic saponins UA and OA showed the highest emulsion stabilizing properties: they decreased CI from 3.26% to 10.23% (p?<?0.05). According to obtained interfacial tension data, the effect of rosemary active ingredients is not surfactant-like. Even though emulsifier itself at low concentration intends to form directly the multiple emulsion, the obtained results indicate that rosemary extract containing active ingredients does not only serve as functional cosmetic agent due to a number of biological activities, but also offer potential advantages as a stabilizer and an enhancer of W/O/W emulsions formation for dermopharmaceutical and cosmetic preparations.     

Water-in-oil-in-water double emulsions loaded with chlorogenic acid: release mechanisms and oxidative stability

Abstract

Chlorogenic acid (CA) is a natural compound used as an antioxidant in the preparation of food, drugs, and cosmetics. Due to their low stability and bioavailability, many researchers have studied the encapsulation of CA in various delivery colloidal systems. The aim of this study was to evaluate the stability of water-in-oil-in-water (W/O/W) double emulsions loaded with CA and its antioxidant capacity. For this purpose, CA-W/O/W double emulsions were prepared using Span 80 and lecithin as lipophilic emulsifiers, and Tween 20 as a hydrophilic emulsifier. The influence of nature of lipophilic emulsifiers, the presence of chitosan (CH) in the internal and external aqueous phases, pH, temperature and the storage time of W/O/W double emulsions were also investigated. Depending on the preparation conditions, the W/O/W double emulsions showed the droplet size in the range 9.13?±?0.55?μm–38.21?±?1.87?μm, the creaming index 34%–78% and the efficiency encapsulation 79.45?±?1.5%–88.13?±?1.9%. Zeta potential values were negative for the W/O/W double emulsion without CH (?36.8?±?2.02mV; ?27.3?±?1.75mV) and positive for the W/O/W double emulsions with CH in the external aqueous phase (+6.5?±?0.42mV; 28.6?±?0.92mV). The study of the release of CA from W/O/W double emulsions has highlighted two mechanisms: one based on the coalescence between the water inner droplets or between the oil globules as well as a diffusion releasing mechanism. The oxidative stability parameters of the W/O/W double emulsions, such as the peroxide value (POV) and the conjugated diene content (CD) were measured.     

The effect of homogenization method on the properties of carbamazepine microparticles prepared by spray congealing

Abstract

The aim of this study was to investigate the influence of ultrasound and high-shear mixing on the properties of microparticles obtained by spray congealing. Dispersions containing 10% carbamazepine and 90% carrier Gelucire® 50/13 (w/w) were prepared using magnetic stirring, high-shear mixing, or ultrasound. Each preparation was made using hot-melt mixing spray congealing to obtain the microparticles. All microparticles presented a spherical shape with high encapsulation efficiency (>99%). High-shear mixing and ultrasound promoted a decrease in the size of microparticles (D₉₀) to 62.8?±?4.1?μm and 64.9?±?3.3?μm, respectively, while magnetic stirring produced microparticles with a size of 84.1?±?1.4?µm. The use of ultrasound led to microparticles with increased moisture content as identified through sorption isotherm studies. In addition, rheograms showed distinct rheological behaviour among different dispersion preparations. Therefore, the technique used to prepare dispersions for spray congealing can affect specific characteristics of the microparticles and should be controlled during the preparation.     

Antioxidant capacity of Typha angustifolia extracts and two active flavonoids

Context: The pollen of Typha angustifolia L. (Typhaceae) has been used as a traditional Chinese medicine for improving the microcirculation and promoting wound healing. Flavonoids are the main constituent in the plant, but little is known about the antioxidant activity of the principal constituent of the pollen in detail.

Objectives: To assess the antioxidant activities of ethanol and water extracts and two constituents of the pollen.

Materials and methods: Plant material (1?g) was extracted by 95% ethanol and water (10?mL?×?2, 1?h each), respectively. The extracted activities (0.8–2.6?mg/mL) were measured by DPPH and the reducing activity of ferric chloride (1.7–2.6?mg/mL). Typhaneoside and isorhamnetin-3-O-neohesperidoside (I3ON) (2.8–70?μmol/L) were investigated on the relationship between NO, MDA and SOD in HUVECs treated with 100?μg/mL of LPS for 24?h.

Results: Nine compounds were identified by UPLC-MS. Ethanol extract showed IC₅₀ values in DPPH (39.51?±?0.72) and Fe³⁺ reducing activity (82.76?±?13.38), higher than the water extract (50.85?±?0.74) and (106.33?±?6.35), respectively. Typhaneoside and I3ON promoted cell proliferation at the respective concentration range of 2.8 to 70?μmol/L (p?p?p?p?Conclusions: The constituents from Typha angustifolia could be a novel therapeutic strategy for LPS-induced inflammation.     

Effect of non–phospholipid-based cationic and phospholipid-based anionic nanosized emulsions on skin retention and anti-inflammatory activity of celecoxib

Context: Celecoxib (CXB, 0.2?g)-loaded anionic and cationic nanosized emulsions were prepared by a well-established combined emulsification method.

Objectives: To investigate the effect of non–phospholipid-based cationic and phospholipid-based anionic emulsions on skin retention and anti-inflammatory activity of CXB.

Methods: Using Keshary-Chien diffusion cells with cellulose acetate membrane or excised rat skin, in vitro release and skin retention of CXB from solution and emulsions were studied. The anti-inflammatory activity was evaluated by the carrageenan-induced hind paw edema method in Wistar rats.

Results: The amount of drug released through artificial membrane has decreased from 122.00?±?0.70?μg/cm² for the CXB solution to 55.80?±?0.70?μg/cm² for anionic emulsion, and then further decreased to 24.79?±?0.90?μg/cm² for cationic emulsion. The J_SS value obtained with solution, anionic, and cationic emulsions were 6825.79?±?920.86, 2513.15?±?382.71, and 1925.67?±?147.42, respectively. Cationic emulsion showed a significantly higher level (P?≤?0.05) of drug accumulation in full-thickness rat skin than anionic emulsion, and a substantially lesser percentage inhibition of edema values compared with both solution and anionic emulsion.

Discussion and conclusion: Sustained drug release together with increased skin accumulation and simultaneously decreased skin permeation as observed with cationic emulsion should substantiate its suitability as a topical delivery vehicle for CXB.     

Development of piperic acid derivatives from Piper nigrum as UV protection agents

Abstract

Context: There is a need for the discovery of novel natural and semi-synthetic sunscreen that is safe and effective. Piperine has a UV absorption band of 230–400?nm with high molar absorptivity. This compound has a high potential to be developed to sunscreen.

Objective: This study develops new UV protection compounds from piperine by using chemical synthesis.

Materials and methods: Piperine was isolated from Piper nigrum L. (Piperaceae) fruits, converted to piperic acid by alkaline hydrolysis, and prepared as ester derivatives by chemical synthesis. The piperate derivatives were prepared as 5% o/w emulsion, and the SPF values were evaluated. The best compound was submitted to cytotoxicity test using MTT assay.

Results: Piperic acid was prepared in 86.96% yield. Next, piperic acid was reacted with alcohols using Steglich reaction to obtain methyl piperate, ethyl piperate, propyl piperate, isopropyl piperate, and isobutyl piperate in 62.39–92.79% yield. All compounds were prepared as 5% oil in water emulsion and measured its SPF and UVA/UVB values using an SPF-290S analyzer. The SPF values (n?=?6) of the piperate derivatives were 2.68?±?0.17, 8.89?±?0.46, 6.86?±?0.91, 16.37?±?1.8, and 9.68?±?1.71. The UVA/UVB ratios of all compounds ranged from 0.860 to 0.967. Cytotoxicity of isopropyl piperate was evaluated using human skin fibroblast cells and the IC₅₀ was equal to 120.2?μM.

Discussion and conclusion: From the results, isopropyl piperate is an outstanding compound that can be developed into a UV protection agent.     

Spirodela polyrhiza extract modulates the activation of atopic dermatitis-related ion channels,Orai1 and TRPV3, and inhibits mast cell degranulation

Context: Spirodela polyrhiza (L.) Schleid. (Lemnaceae), Spirodelae Herba (SH), has been known to relieve inflammation, urticaria and skin symptoms including pruritus, eczema and rash.

Objective: The effects of SH extract on two calcium ion channels, Orai1 and TRPV3, and their potential as novel therapeutics for atopic dermatitis (AD) were investigated. The regulatory role of Orai1 on mast cell degranulation was evaluated.

Materials and methods: The dried leaves of SH were extracted by 70% methanol. Effects of SH extract (100?μg/mL) in an HEK293T cell line overexpressing human Orai1 or TRPV3 were assessed. Ion channel modulation in transfected HEK293T cells was measured using a conventional whole-cell patch-clamp technique. IgE-antigen complex-stimulated mast cell degranulation was measured by β-hexosaminidase assay with morphological observation after treatment with 20, 50 and 100?μg/mL SH extract.

Results: SH extract (100?μg/mL) significantly inhibited Orai1 activity (63.8?±?0.97%) in Orai1-STIM1 co-overexpressed HEK293T cells. SH extract significantly increased TRPV3 activity (81.29?±?0.05% at ?100?mV) compared with the positive control 2-APB (100?μM), which induced full activation. SH extract inhibited degranulation in IgE-antigen complex-stimulated RBL-2H3 mast cells by decreasing β-hexosaminidase activity (3.14?±?0.03, 2.56?±?0.12 and 2.29?±?0.08?mU/mg, respectively).

Conclusion: Our results suggested that SH extract could treat abnormal skin barrier pathologies in AD through modulation of the activities of the calcium ion channels Orai1 and TRPV3 and inhibition of mast cell degranulation. This is the first report of an herbal effect on the modulation of ion channels associated with skin barrier disruption in AD pathogenesis.     

Evaluation of anti-inflammatory activity and standardisation of hydro-methanol extract of underground tuber of Dioscorea alata

Context The underground edible tuber of Dioscorea alata L. (Dioscoreaceae) is a functional food with high nutritive value and therapeutic potential. The tuber is known to possess anti-inflammatory properties in traditional medicine.

Objective The present study explores the anti-inflammatory activity and standardisation of D. alata tuber hydromethanol extract.

Materials and methods Hydromethanol extract (70%) of D. alata tuber was chemically characterised using HPLC and GC-MS techniques. Murine lymphocytes were cultured for 48?h with six different concentrations (0–80?μg/mL) of the extract. The expression of nitric oxide (NO), TNF-α, COX-1, COX-2, and PGE₂ were evaluated using colorimetric and ELISA methods.

Results Dioscorea alata extract inhibited the expression of NO and TNF-α with an IC₅₀ value of 134.51?±?6.75 and 113.30?±?7.44?μg/mL, respectively. The IC₅₀ values for inhibition of total COX, COX-1, COX-2 activities and PGE₂ level were 41.96?±?3.07, 141.41?±?8.99, 32.50?±?1.69, and 186.34?±?15.36?μg/mL, respectively. Inhibition of PGE₂ level and COX-2 activity was positively correlated (R²?=?0.9393). Gallic acid (GA), 4-hydroxy benzoic acid (4HBA), syringic acid (SYA), p-coumaric acid (PCA), and myricetin (MY) were identified and quantified using HPLC. GC-MS analysis revealed the presence of 13 different phytocompounds such as hexadecanoic acid, methyl stearate, cinnamyl cinnamate, and squalene.

Conclusion The D. alata extract significantly down-regulated the pro-inflammatory signals in a gradual manner compared with control (0?μg/mL). Different bioactive phytocompounds individually possessing anti-inflammatory activities contributed to the overall bioactivity of the D. alata tuber extract.     

Epigallocatechin-3-gallate counters cisplatin toxicity of rat testes

Context: Epigallocatechin-3-gallate (EG), the main active flavonoid in green tea, has well-known anti-inflammatory, antioxidant, and anti-apoptotic activities.

Objective: The EG protection against testicular injury induced by cisplatin was studied in Sprague–Dawley rats.

Materials and methods: Cisplatin (10?mg/kg, i.p) was given as a single injection to rats. EG was given at 40 and 80?mg/kg/day, i.p., for 5 days, starting the same day of cisplatin insult. Serum testosterone, and testicular malondialdehyde, total antioxidant status, nitric oxide, interleukin-6, interleukin-1β, cytochrome C, Bax/Bcl-2 ratio, and caspase-3 were measured. In addition, testicular histopathological examination and immunohistochemical expression of testicular tumour necrosis factor-α were evaluated.

Results: Cisplatin, compared to the control, significantly decreased serum testosterone (6.48?±?0.7 vs. 50.8?±?4.91?ng/10?mL), and testicular tissue antioxidant status (17.3?±?1.21 vs. 64.12?±?5.4?μmol/g), and significantly increased interleukin-6 (85.81?±?6.11 vs. 38.2?±?2.79?pg/100?mg), interleukin-1β (98.09?±?8.31 vs. 32.52?±?2.08?pg/100?mg), malondialdehyde (74.5?±?5.88 vs. 23.8?±?1.91?nmol/g), nitric oxide (104.98?±?8.5 vs. 52.68?±?5.12?nmol/100?mg), cytochrome C (5.97?±?0.33 vs. 1.6?±?0.99?ng/mg protein), Bax/Bcl-2 ratio (4.01?±?0.38 vs. 0.71?±?0.0), and caspase-3 (3.2?±?0.21 vs. 0.98?±?0.08?O.D. 405?nm) in rat testes. EG (40 and 80?mg/kg, respectively) caused significant increases of serum testosterone (33.9?±?2.89 and 47.88?±?4.4?ng/10?mL), and testicular antioxidant status (47.1?±?3.92 and 58.22?±?3.58?μmol/g), and significant decreases of interleukin-6 (57.39?±?4.2 and 48.18?±?3.98?pg/100?mg), interleukin-1β (65.12?±?5.88 and 41.96?±?3.51?pg/100?mg), malondialdehyde (42.3?±?3.9 and 28.67?±?2.49?nmol/g), nitric oxide (70.6?±?6.79 and 61.31?±?5.18?nmol/100?mg), cytochrome C (3.4?±?0.27 and 2.21?±?0.18?ng/mg protein), Bax/Bcl-2 ratio (1.49?±?0.14 and 1.1?±?0.09), and caspase-3 (2.1?±?0.17 and 1.48?±?0.13?O.D. 405?nm) in testes of cisplatin-treated rats. Additionally, both doses of EG significantly ameliorated the histopathological injury and reduced tumour necrosis factor-α expression in rat testes.

Conclusion: EG can afford testicular protection in cisplatin-challenged rats by its antioxidant, antinitrative, anti-inflammatory and antiapoptotic effects.     

Gelidiella acerosa protects against Aβ 25–35-induced toxicity and memory impairment in Swiss Albino mice: an in vivo report

Context: Alzheimer’s disease (AD) is believed to develop due to deposition of β-amyloid (Aβ) peptide. Hence, efforts are being made to develop potent drug that target amyloid hypothesis.

Objective: The present study explores the effect of the seaweed Gelidiella acerosa (Forsskål) Feldmann &; Hamel (Gelidiellaceae) against Aβ 25–35 peptide in Swiss albino mice.

Materials and methods: The animals were administered through intracerebroventricular (ICV) injection with the Aβ 25–35 peptide (10?μg/10?μL/ICV site) on 21st day of the pretreatment of G. acerosa (whole plant) benzene extract (200 and 400?mg/kg bw). On day 30, animals were sacrificed and brain tissue homogenate was prepared. The activities of AChE, BuChE, b-secretase, MAO-B, and caspase-3 were determined, and Bax expression was assessed by Western blotting.

Results: Gelidiella acerosa benzene extract restored the level of antioxidant enzymes and prevented lipid and protein oxidation significantly (p?<?0.05). The extract protected the mice from cholinergic deficit significantly (p?<?0.05) by inhibiting the activities of AChE and BuChE, which was about 0.116?±?0.0088?U/mg of protein and 0.011?±?0.0014?U/mg of protein respectively, which was otherwise increased in peptide-treated group (0.155?±?0.007?U/mg of protein and 0.015?±?0.0012?U/mg of protein respectively). Interestingly, G. acerosa benzene extract inhibited β-secretase and MAO-B activity. Reduction (p?<?0.05) in level of caspase-3 activity and Bax expression suggests that G. acerosa protects the cells from apoptosis.

Discussion and conclusion: The results suggest that G. acerosa possesses excellent neuroprotective potential against peptide mediated toxicity under in vivo conditions.     

Indirect modulation of the endocannabinoid system by specific fractions of nutmeg total extract

Context: Nutmeg [Myristica fragrans Houtt. (Myristicaceae)] has a long-standing reputation of psychoactivity. Anecdotal reports of nutmeg use as a cheap marijuana substitute, coupled to previous studies reporting a cannabimimetic-like action, suggest that nutmeg may interact with the endocannabinoid system.

Objective: The study evaluates nutmeg fractions for binding capacity with various CNS receptors and their potential interaction with the endocannabinoid system.

Materials and methods: Dichloromethane (DF) and ethyl acetate (EF) fractions were prepared from the methanol extract of powdered whole nutmeg. The HPLC-profiled fractions were assayed by the NIMH Psychoactive Drug Screening Program (PDSP) in a panel of CNS targets at a 10?μg/mL concentration. The fractions were also screened for fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition, initially at a concentration of 500?μg/mL, then by concentration-dependent inhibition studies.

Results: None of the tested fractions showed significant binding to CNS receptors included in the PDSP panel. However, both fractions exerted significant inhibition of the FAAH and MAGL enzymes. The DF fraction inhibited FAAH and MAGL enzymes at IC₅₀ values of 21.06?±?3.16 and 15.34?±?1.61?μg/mL, respectively. Similarly, the EF fraction demonstrated FAAH and MAGL inhibition with IC₅₀ values of 15.42?±?3.09 and 11.37?±?6.15?μg/mL, respectively.

Discussion and conclusion: The study provides the first piece of evidence that nutmeg interacts with the endocannabinoid system via inhibition of the endocannabinoid catabolizing enzymes. This mechanism provides insight into reported cannabis-like action as well as expands the potential therapeutic utility of nutmeg.     

Mechanism of ginsenoside Rg1 renal protection in a mouse model of d-galactose-induced subacute damage

Context Ginseng is a widely used herbal medicine in China but its mechanism of action remains unclear.

Objective The objectives of this work were to study the protective effect of ginsenoside Rg1 on subacute murine renal damage induced by d-galactose and its mechanism.

Materials and methods C57BL/6J mice were injected with 120?mg/kg/d (sc) d-galactose for 1 week, followed by a combined treatment of Rg1 20?mg/kg/d (ip) and 120?mg/kg/d d-galactose (sc) for 5 weeks. Mice were injected with the 0.9% saline 0.2?mL/d (sc) and 120?mg/kg/d d-galactose (sc) for 6 weeks in the control group and the d-galactose group, respectively. After 6 weeks, urea, creatinine, uric acid, cystatin (Cys-C), senescence-associated β-galactosidase (SA-β-gal) staining positive kidney cells, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG) were measured.

Results Treatment with Rg1 ameliorated kidney function and aging state (urea from 17.19?±?1.09 to 15.77?±?1.22?mmol·L?^??¹, creatinine from 29.40?±?5.72 to 22.60?±?3.97?μmol·L?^??¹, uric acid from 86.80?±?5.97 to 72.80?±?10.61?μmol·L?^??¹, Cys-C from 0.23?±?0.03 to 0.18?±?0.05?mg·L?^??¹, ROD of SA-β-gal from 56.32?±?10.48 to 26.78?±?7.34, SOD from 150.22?±?19.07 to 190.56?±?15.83 U·(mg·prot)?^?1, MDA from 9.28?±?1.59 to 3.17?±?0.82?nmol·(mg·prot)?^?1, GSH-PX from 15.68?±?2.11 to 20.32?±?2.96 U·(mg·prot)?^?1 as well as regulated glomerulus morphology (glomerulus diameter from 775.77?±?18.41 to 695.04?±?14.61?μm, renal capsule width from 39.56?±?3.51 to 31.42?±?2.70?μm, glomerulus basement membrane from 206.03?±?16.22 to 157.27?±?15.70?nm, podocyte slit from 55.21?±?8.55 to 37.63?±?6.65?nm).

Conclusions Ginsenoside Rg1 can antagonise d-galactose subacute renal damage in mice and this may occur due to alleviating oxidative stress injury.     

Anti-Helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats

Context: Peptic ulcer is one of the most common diseases affecting mankind. Although there are many products used for its treatment, most of these products produce severe adverse reactions requiring the search for novel compounds. Some Afromomum species are used traditionally to cure acute gastritis.

Objective: To evaluate the antiulcer activity of the methanol extract of Aframomum pruinosum Gagnepain (Zingiberaceae) seeds against two major etiologic agents of peptic ulcer disease; Helicobacter pylori and non-steroidal anti-inflammatory drugs.

Materials and methods: The anti-Helicobacter activity of A. pruinosum was evaluated using the broth microdilution method. After oral administration of indomethacin (5?mg/kg) for 5 consecutive days, gastric ulcerated animals were divided into control group and five other groups: three groups that recieved respectively 125, 250 and 500?mg/kg of plant extract, the fourth group received Maalox (50?mg/kg) and the fifth group, Misoprostol (100?μg/kg), respectively, for 5 days. Ulcer areas, gastric mucus content and nitric oxide gastric levels of animals were assessed 24?h after this treatment.

Results: A. pruinosum extract shows a moderate anti-Helicobacter activity with an MIC value of 128?μg/mL. A. pruinosum extract, like Misoprostol and Maalox, markedly reduces the % of ulcerated area from 8.15?±?0.33 to 1.71?±?0.44% (500?mg/kg). It also increased significantly mucus and NO gastric production with respective values of 4.44?±?1.35 and 965.81?±?106.74?μmol/g (500?mg/kg).

Discussion and conclusion: These findings suggest that A. pruinosum methanol extract possesses antiulcer properties as ascertained by the comparative decreases in ulcer areas, increase of mucus and NO gastric production.     

Treatment of Helicobacter pylori infected mice with Bryophyllum pinnatum,a medicinal plant with antioxidant and antimicrobial properties,reduces bacterial load

Context: Bryophyllum pinnatum (Lam.) Kurz (Crassulaceae) is a plant known for its antiulcer properties.

Objective: This study evaluates the anti-Helicobacter pylori activity of Bryophyllum pinnutum methanol extract with a mouse model and its antioxidant properties.

Materials and methods: Dried leaves of Bryophyllum pinnutum were extracted with methanol and ethyl acetate. Broth microdilution method was used to evaluate the anti-Helicobacter activity of extract samples in vitro. Swiss mice were inoculated with a suspension of Helicobacter pylori and divided into control group and four others that received 125, 250, 500?mg/kg of methanol extract or ciprofloxacin (500?mg/kg), respectively, for 7 days. Helicobacter pylori colonization and bacterial load of mouse stomach was assessed on day 1 and 7 post-treatment. The antioxidant activity of Bryophyllum pinnutum was evaluated through DPPH radical, hydroxyl radical and reducing power assay.

Results: Methanol extract showed a significant anti-Helicobacter activity with MIC and MBC values of 32 and 256?μg/mL, respectively. Bryophyllum pinnatum and ciprofloxacin reduced H. pylori colonization of gastric tissue from 100% to 17%. Bryophyllum pinnatum extract (85.91?±?52.91 CFU) and standard (25.74?±?16.15 CFU) also reduced significantly (p?50 values of 25.31?±?0.34, 55.94?±?0.68 and 11.18?±?0.74?μg/mL, respectively.

Discussion and conclusion: The data suggest that the methanol extract of Bryophyllum pinnatum could inhibit Helicobacter pylori growth, and may also acts as an antioxidant to protect gastric mucosa against reactive oxygen species.     

Antioxidant properties of Ferulago angulata and its hepatoprotective effect against N-nitrosodimethylamine-induced oxidative stress in rats

Context: Ferulago angulata (Schlecht.) Boiss. (Apiaceae) (FASB) is used to treat liver diseases and has been used both as food and therapeutics by many cultures for thousands of years because of the natural antioxidant compounds.

Objective: This study determines antioxidant properties of FASB flowers, the levels of minerals and vitamins, and also, evaluates the hepatoprotective effect of flowers against N-nitrosodimethylamine (NDMA) induced on liver tissue by assessing antioxidant enzymes and histopathological parameters in Wistar albino rats.

Materials and methods: In the study, the rats were divided into six groups of ten. Control, untreated animals were given 0.9% NaCl. Rats were intraperitoneally given NDMA (10?mg/kg) for the first 7 days. FASB methanol extract (150 and 300?mg/kg) was administered orally for 21 days.

Results: α-Tocopherol, retinol, ascorbic acid, total antioxidant activity, phenolic and flavonoid contents of FASB were 0.70?±?0.13, 0.29?±?0.03?μg/g, 139.32?±?7.06?μg/100?g, 171.61?±?6.05?mM ascorbic acid/g, 90.47?±?4.11?mg GA/g and 37.39?±?2.85?mg QE/g. DPPH and hydroxyl radical scavenging activity was obtained IC₅₀ 67.34?±?4.14 and 64.87?±?4.68?μg/mL, respectively.

Discussion and conclusion: The results of the study indicated that FASB flowers contain high levels of vitamins, minerals, total antioxidant activity, phenolics and flavonoids. Due to the positive effect on significant changes in antioxidant enzymes of liver tissue and histopathological examination, it is thought that the plant could be used as a hepatoprotective.     

Psoralea corylifolia extract induces vasodilation in rat arteries through both endothelium-dependent and -independent mechanisms involving inhibition of TRPC3 channel activity and elaboration of prostaglandin

Context: Fructus Psoralea, Psoralea corylifolia L. (Leguminosae), has been widely used in traditional medicines for the treatment of dermatitis, leukoderma, asthma and osteoporosis.

Objectives: In this study, we sought to study mechanisms underlying the vasoactive properties of Psoralea corylifolia extract (PCE) and its active ingredients.

Materials and methods: To study mechanisms underlying the vasoactive properties of PCE prepared by extracting dried seeds of Psoralea corylifolia with 70% ethanol, isometric tension recordings of rat aortic rings and the ionic currents through TRPC3 (transient receptor potential canonical 3) channels were measured with the cumulative concentration (10–600?μg/mL) of PCE or its constituents.

Results: Cumulative treatment with PCE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC₅₀ values of 61.27?±?3.11 and 211.13?±?18.74?μg/mL, respectively. Pretreatment with inhibitors of nitric oxide (NO) synthase, guanylate cyclase, or cyclooxygenase and pyrazole 3, a selective TRPC3 channel blocker, significantly decreased PCE-induced vasorelaxation (p?50 128.9, 4.5, 32.1 and 114.9?μg/mL, respectively).

Discussion and conclusions: Taken together, our data indicate that the vasodilatory actions of PCE are dependent on endothelial NO/cGMP and also involved in prostaglandin production. PCE and its active constituents, bakuchiol, isobavachalcone, isopsoralen and psoralen, caused dose-dependent inhibition of TRPC3 channels, indicating that those ingredients attenuate Phe-induced vasoconstriction.     

Microencapsulation of insulin using a W/O/W double emulsion followed by complex coacervation to provide protection in the gastrointestinal tract

Abstract

Microcapsules containing insulin were prepared using a combination of a W/O/W double emulsion and complex coacervation between WPI (used as a hydrophilic emulsifier) and CMC or SA with further spray drying of the microcapsules in order to provide protection in the gastrointestinal tract. The microcapsules prepared exhibited high encapsulation efficiency and showed the typical structure of a double emulsion. After spray drying of these microcapsules, the integrity of the W/O/W double emulsion was maintained and the biological residual activity remained high when using the combination of 180?°C inlet air temperature and 70?°C outlet air temperature. The microcapsules exhibited low solubility at pH 2 and high solubility at pH 7 so they might protect insulin at acid pH values in the stomach and release it at intestinal pH values. The microcapsules developed in this study seem to be a promising oral delivery vehicle for insulin or other therapeutic proteins.     

RETRACTED ARTICLE: Preparation and characterization of novel lipid nanocapsules of ropivacaine for transdermal delivery

Abstract

Ropivacaine, a novel long-acting local anesthetic, has been proved to own superior advantage. However, the application form used in clinic, ropivacaine hydrochloride (Naropin® Injection), which should be administed intravenously, is causing poor patient convenience. The purpose of this study was to formulate ropivacaine (RPV) in lipid nanocapsules (LNCs) and character the potential of LNCs in delivering RPV transdermally to exploit novel external preparation. The RPV-LNCs were successfully prepared by phase inversion technique and the formulation was characterized in terms of size, zeta potential, ex vivo permeation study, and pharmacodynamics. The prepared RPV-LNCs displayed a typical core-shell structure with a narrow size distribution of 62.1?±?1.7?nm and drug loading of 1.35?±?0.20%. The results of differential scanning calorimetry (DSC) analysis and X-ray diffraction showed that RPV was in amorphous crystalline state when encapsulated into LNCs. Furthermore, the results of ex vivo permeation study displayed that RPV-LNCs had an improved permeability (349.0?±?11.5?μg?cm^?2 versus 161.0?±?1.3?μg?cm^?2) compared with free RPV. The results of histopathology study showed that interaction between LNCs and skin could break the close conjugation of corneocyte layers. In the mice writhing test, RPV-LNCs exhibited obvious analgesic effect by both prolonging pain latency and reducing the writhing response with an inhibition rate of 91.3% compared to the control group. In conclusion, RPV-LNCs could be a promising delivery system to encapsulate RPV and deliver RPV for transdermal administration.     

Preparation and evaluation of dl-praeruptorin A microemulsion based hydrogel for dermal delivery

Abstract

The purpose of the present investigation was to develop and optimize the microemulsion (ME) as a transdermal system for Pd-Ia, a poor water soluble and low bioavailable drug. The pseudo-ternary phase diagrams were constructed for various ME formulations including oleic acid as the oil phase, Cremophor RH40 as the surfactant, ethanol as the cosurfactant, and water. The maximum cumulative amount permeated through rat abdominal skins per unit area in 32?h (Q₃₂), and the maximum flux were evaluated using the Franz diffusion cell in order to optimize the ME formulation. The results indicated that the optimized ME formulation was composed of oleic acid (5%, W/W), Cremophor RH40 (13.33%, W/W), ethanol (26.67%, W/W), and water (55%, W/W); the maximum cumulative amount of Pd-Ia was 354.330?±?12.006?μg?cm^?2, the maximum flux was 11.467?±?0.500?μg?cm^?2?h^?1. ME-gel was administered transdermally to rats. The mean plasma concentration of Pd-Ia following transdermal application of ME-gel could be maintained for 32?h at least and the half-life was evidently prolonged. It shows that the ME-gel could be a promising vehicle for dermal delivery of Pd-Ia.     

Dissolving microneedles to obtain rapid local anesthetic effect of lidocaine at skin tissue

Abstract

Dissolving microneedles (DMs) were applied to lidocaine for local anesthesia of the skin. Three DM array chips were prepared where lidocaine was localized at the acral portion of DMs (type 1), loaded in whole DMs (type 2), and lidocaine was loaded both in whole DMs and the chip (type 3). DM chips were 15-mm diameter with 225 DMs, each 500-μm long with a 300-μm diameter base. The lidocaine contents were (type 1) 0.08?±?0.01?mg, (type 2) 0.22?±?0.01?mg and (type 3) 8.52?±?0.49?mg. Lidocaine was released from type 1 and 2 DM array chips within 10?min. Pharmacological activity of DMs were compared to lidocaine cream by the suppression of idiospasm of hair-removed rat skin. Type 1, 2 and 3 DMs showed faster onset time, 5?min, than lidocaine cream. Type 2 and 3 DMs showed stronger anti-idioplasmic activity than type 1 DMs. Pharmacokinetic study showed that tissue lidocaine levels, 62.8?±?3.6 (type 1), 89.1?±?9.9 (type 2) and 131.2?±?10.2(type 3) μg/g wet weight at 5?min after the removal of DM were obtained higher than lidocaine cream, 26.2?±?12.5?μg/g wet weight. Those results suggest the usefulness of type 2 DMs to obtain fast onset time for the local anesthesia in the skin.