Antioxidant, carbonic anhydrase inhibition and diuretic activity of Leptadenia pyrotechnica Forssk. Decne.

Background: Leptadenia pyrotechnica Forssk. Decne is a member of family Apocynaceae and locally known as 'Khipp'. It is found in dry, sandy habitat of Pakistan and in several other regions around the world including Asia, Tropical Africa, Western Gulf and Mediterranean countries. It has nutritional value, containing 4 % lipids, 23 % proteins, 28 % carbohydrates, 4 % fibers, vitamin E and several minerals. Traditionally, this plant has been used by several communities for pain, different inflammatory and kidney disorders. Ethno-botanical studies have reported the use of L. pyrotechnica in nephrolithiasis, kidney disorders and induction of diuresis, which requires a detailed pharmacological study to validate the folkloric use of L. pyrotechnica as diuretic. Methods: The 70 % methanolic L. pyrotechnica (Lp.Cr) extract was prepared and qualitatively checked for the presence of various phytochemicals. Phenolic, flavonoid, tannin and saponin contents were quantified. GC-MS analysis of Lp.Cr was also performed. Antioxidant potential of Lp.Cr was evaluated by DPPH, ABTS and nitrite radical scavenging assays. CUPRAC and FRAP assay described the reducing potential of Lp.Cr. Diuretic activity was performed in both acute and prolonged models at different doses followed by the estimation of electrolytes, urea and creatinine levels. The mechanism of diuresis was described by pre-treatment with atropine, l-NAME, indomethacin and carbonic anhydrase inhibition. Results: Lp.Cr. indicated high phenolic and flavonoid contents which correlated with good antioxidant activity. GC-MS analysis showed the presence of 104 compounds from different phytochemical classes. Diuretic activity was performed at 10-300 mg/kg concentrations where the dose of 100 and 300 mg/kg showed good diuretic and saluretic activity comparable to furosemide. Lp.Cr exhibited diuresis both in acute and prolonged study protocols which can be attributed to carbonic anhydrase inhibition, effect on prostaglandins and cholinergic pathways. Conclusion: L. pyrotechnica contained several phytochemicals and exhibited good antioxidant activity. It induced diuresis and saluretic activity which was comparable to furosemide at higher doses. Diuretic activity can be attributed to carbonic anhydrase inhibition, prostaglandin synthesis and cholinergic pathways.

Tioconazole-Loaded Transethosomal Gel Using Box-Behnken Design for Topical Applications: In Vitro, In Vivo, and Molecular Docking Approaches.

Tioconazole (TCZ) is a broad-spectrum fungicidal BCS class II drug with reported activity against Candida albicans, dermatophytes, and certain Staphylococci bacteria. We report the use of TCZ-loaded transethosomes (TEs) to overcome the skin's barrier function. TCZ-loaded TEs were fabricated by using a cold method with slight modification. Box-Behnken composite design was utilized to investigate the effect of independent variables. The fabricated TEs were assessed with various physicochemical characterizations. The optimized formulation of TCZ-loaded TEs was incorporated into gel and evaluated for pH, conductivity, drug content, spreadability, rheology, in vitro permeation, ex vivo permeation, and in vitro and in vivo antifungal activity. The fabricated TCZ-loaded TEs had a % EE of 60.56 to 86.13, with particle sizes ranging from 219.1 to 757.1 nm. The SEM images showed spherically shaped vesicles. The % drug permeation was between 77.01 and 92.03. The kinetic analysis of all release profiles followed Higuchi's diffusion model. The FTIR, DSC, and XRD analysis showed no significant chemical interactions between the drug and excipients. A significantly higher antifungal activity was observed for TCZ-loaded transethosomal gel in comparison to the control. The in vivo antifungal study on albino rats indicated that TCZ-loaded transethosomal gel showed a comparable therapeutic effect in comparison to the market brand Canesten®. Molecular docking demonstrated that the TCZ in the TE composition was surrounded by hydrophobic excipients with increased overall hydrophobicity and better permeation. Therefore, TCZ in the form of transethosomal gel can serve as an effective drug delivery system, having the ability to penetrate the skin and overcome the stratum corneum barrier with improved efficacy.

Anti-inflammatory, anti-nociceptive and anti-pyretic activities of Cenchrus ciliaris L.

ETHNOPHARMACOLOGICAL RELEVANCE: Cenchrus ciliaris L. belongs to the family Poaceae and is found all over the world. It is native to the Cholistan desert of Pakistan where it is locally known as 'Dhaman'. Owing to high nutritional value, C. ciliaris is used as fodder while seeds are used for bread making which are consumed by locals. It also possesses medicinal value and is extensively employed to treat pain, inflammation, urinary tract infection, and tumors. AIM OF STUDY: Studies on the pharmacological activities of C. ciliaris are scarce in spite of its several traditional uses. To the best of our knowledge, no comprehensive study has been conducted on anti-inflammatory, analgesic and anti-pyretic activity of C. ciliaris until now. Here we employed an integrative phytochemical and in - vivo framework to evaluate the potential biological activities of C. ciliaris against inflammation, nociception and pyrexia experimentally induced in rodents. MATERIAL AND METHODS: C. ciliaris was collected from the desert of Cholistan, Bahawalpur, Pakistan. Phytochemical profiling of C. ciliaris was done by employing GC-MS analysis. Anti-inflammatory activity of plant extract was initially determined by various in - vitro assays including albumin denaturation assay and RBC membrane stabilization assays. Finally, rodents were utilized to evaluate in - vivo anti-inflammatory, antipyretic and anti-nociceptive activities. RESULTS: Our data revealed the presence of 67 phytochemicals in methanolic extract of C. ciliaris. The methanolic extract of C. ciliaris provided RBC membrane stabilization by 65.89 ± 0.32% and protection against albumin denaturation by 71.91 ± 3.42% at 1 mg/ml concentration. In in - vivo acute inflammatory models, C. ciliaris exhibited 70.33 ± 1.03, 62.09 ± 8.98, 70.24 ± 0.95% anti-inflammatory activity at concentration of 300 mg/ml against carrageenan, histamine and serotonin induced inflammation. In CFA induced arthritis, inhibition of inflammation was found to be 48.85 ± 5.11% at 300 mg/ml dose after 28 days of treatment. In anti-nociceptive assays C. ciliaris exhibited significant analgesic activity in both peripheral and centrally mediated pain. The C. ciliaris also reduced the temperature by 75.26 ± 1.41% in yeast induced pyrexia. CONCLUSION: C. ciliaris exhibited anti-inflammatory effect against acute and chronic inflammation. It also showed significant anti-nociceptive and anti-pyretic activity which endorses its traditional use in the management of pain and inflammatory disorders.

Formulation and characterization of Anacyclus Pyrethrum Emulgels and its in vitro and in vivo evaluation as cosmeceutical product.

BACKGROUND: Plants containing high phenolic and flavonoids contents used widely as antioxidant agent by reducing skin photo damaging effects and play important role in skin rejuvenating. AIMS: This study was performed to explore the cosmetic effects of Anacyclus Pyrethrum extract and to develop stable oil in water (O/W) emulsion base gel loaded with Anacyclus Pyrethrum 10% extract. OBJECTIVE: To explore and quantify phenols and flavonoids present in Anacyclus Pyrethrum extract and determine its cosmetic effects on human skin. METHOD: Emulgel formulation were developed by mixing o/w emulsion with carbopol gelling agent loaded with Anacyclus Pyrethrum (AP) extract and base gel without AP extract. In vitro study was done for the evaluation of color change, liquefaction, hardness, and pH change at different storage condition for the duration of 12 weeks. For in vivo study, emulgel applied on 13 healthy human volunteer's cheeks to evaluate its cosmetics effects and compared with placebo (base). Facial parameters including skin melanin, redness, sebum, moisture content, and skin elasticity were determined by using mexameter, sebumeter, corneometer, elastometer for the study duration of 12 weeks. RESULTS: Total phenolic content in Anacyclus Pyrethrum extract was 80.04 ± 0.0043 mg GAE/g, and flavonoids were 54.64 ± 0.0076 mg QE/g. Anacyclus Pyrethrum extract found significantly effective in reducing skin photo-damage effects (p ≤ 0.05) as compared base gel. CONCLUSION: Anacyclus Pyrethrum extract being rich source of flavonoid and phenolic content, acts as strong antioxidant to protect skin against photo-damaging effect and improve skin conditions.

Fabrication and Evaluation of Voriconazole Loaded Transethosomal Gel for Enhanced Antifungal and Antileishmanial Activity.

Voriconazole (VRC) is a broad-spectrum antifungal agent belonging to BCS class II (biopharmaceutical classification system). Despite many efforts to enhance its solubility, this primary issue still remains challenging for formulation scientists. Transethosomes (TELs) are one of the potential innovative nano-carriers for improving the solubility and permeation of poorly soluble and permeable drugs. We herein report voriconazole-loaded transethosomes (VRCT) fabricated by the cold method and followed by their incorporation into carbopol 940 as a gel. The prepared VRCT were evaluated for % yield, % entrapment efficiency (EE), surface morphology, possible chemical interaction, particle size, zeta potential, and polydispersity index (PDI). The optimized formulation had a particle size of 228.2 nm, a zeta potential of -26.5 mV, and a PDI of 0.45 with enhanced % EE. Rheology, spreadability, extrudability, in vitro release, skin permeation, molecular docking, antifungal, and antileishmanial activity were also assessed for VRCT and VRC loaded transethosomal gel (VTEG). Ex-vivo permeation using rat skin depicted a transdermal flux of 22.8 µg/cm2/h with enhanced efficiency up to 4-fold. A two-fold reduction in inhibitory as well as fungicidal concentration was observed against various fungal strains by VRCT and VTEG besides similar results against L-donovani. The development of transethosomal formulation can serve as an efficient drug delivery system through a topical route with enhanced efficacy and better patient compliance.

Development, characterization, and clinical investigation of Spinacia oleracea-based ultra-high pressure homogenized emulsion system for facial physiological parameters.

BACKGROUND: Spinacia oleracea (SO) exhibits radical scavenging and tyrosinase inhibition activity indicating potential as a depigmenting agent. AIMS: To develop and characterize a stable emulsified system containing SO extract through ultra-high pressure homogenization, evaluate skin permeability, and enumerate in vivo performance in terms of melanin index, skin spots analysis, and related skin physiological parameters. METHOD: Free radical scavenging and tyrosinase inhibition potential of SO extract was quantified through DPPH radical scavenging and mushroom tyrosinase inhibition assay, respectively. Six SO extract loaded ultra-high pressure emulsified systems (UHSO) were developed using ultra-high pressure homogenizer and assessed for size and polydispersity index (PDI). Among the prepared formulations, the optimized formulation (UHSO6) was subjected to 90 days stability studies performed at 8°C, 25°C, 40°C, and 40°C+75% RH (relative humidity) for organoleptic features, pH, and rheology. Ex vivo skin permeability studies were performed on abdominal skin from male albino rat. Changes in skin physiological parameters were evaluated in healthy female volunteers (n = 13) for 12 weeks utilizing mexameter® , corneometer® , and sebumeter® . Skin spots were analyzed through computerized analysis of high-resolution images by visioFace® . RESULTS: SO extract exhibited promising antioxidant (88±0.0096%) and tyrosinase inhibition potential (90.6 ± 0.0015 mg of Kojic Acid Eq/g of extract). Optimized UHSO was found to be stable with respect to stability evaluation, globule size (1110 nm), zeta potential (-27.6), and PDI (0.34). Ex vivo skin permeation of UHSO was significantly higher than SO loaded coarse emulsion. Moreover, the formulation showed a significant decrease in skin melanin, spot count, and spot % area, whereas skin hydration index was improved significantly. CONCLUSION: Stable SO extract loaded emulsion system was successfully developed by a novel, cost-effective technique of ultra-high pressure homogenization which showed improved performance in terms of skin permeation and other skin physiological parameters.

Formulation Development, Characterization, and Evaluation of a Novel Dexibuprofen-Capsaicin Skin Emulgel with Improved In Vivo Anti-inflammatory and Analgesic Effects.

Transdermal application of analgesics allows efficient and painless delivery of medication with minimum side effect. This study was designed with the aim to formulate and characterize dexibuprofen-capsaicin emulgel for transdermal drug delivery with improved anti-inflammatory and analgesic effects. The emulgel was prepared and evaluated for physical examination, stability, spreadability, rheological behavior, viscosity, drug content determination, FTIR analysis, and ex vivo studies. Anti-inflammatory (carrageenan-induced paw edema) and analgesic (hot plate latency test) effects were determined in Sprague-Dawley rats. The dexibuprofen-capsaicin emulgel showed good physical appearance and stability having average pH 5.5 to 6.0, conductivity 73-76 s/m, spreadability (12-)17 g cm/s, drug content 102.84% ± 0.53 (for capsaicin) and 94.09% ± 0.41 (for dexibuprofen), and FTIR compatibility. It was noted that 86.956% ± 1.46 (with 100 mg menthol), 76.687% ± 1.21 (75 mg menthol), and 65.543% ± 1.71 (without menthol) of capsaicin were released. Similarly 81.342% ± 1.21 (with 100 mg menthol), 72.321% ± 1.31 (75 mg menthol), and 52.462% ± 1.23 (without menthol) of dexibuprofen were released. The cumulative amount of capsaicin permeated through rabbit skin was 9.83 ± 0.037 µg/cm2 with 100 mg menthol (as permeation enhancer), 7.23 ± 0.037 µg/cm2 with 75 mg menthol, and 2.23 ± 0.061 µg/cm2 without menthol after 6.5 h. The permeation of dexibuprofen was 19.53 ± 0.054 µg/cm2, 13.87 ± 0.032 µg/cm2, and 3.83 ± 0.074 µg/cm2. Carrageenan-induced paw edema of rat was effectively inhibited by the optimized emulgel. Similarly it was observed that DCE5 shows higher analgesic activity compared with marketed diclofenac sodium emulgel (Dicloran®). The conclusion of this research study evidently indicated a promising synergistic potential of dexibuprofen-capsaicin emulgel as an alternative to the conventional topical dosage form.

Development, characterization and evaluation of anti-fungal activity of miconazole based nanogel prepared from biodegradable polymer.

Topical candidiasis is a known skin fungal infection which is usually treated by conventional dosage forms such as cream, gel, emulgel which are having numerous adverse effects on skin. To overcome such disadvantages, different novel drug delivery systems have been considered. Polymer based nano-particulate systems have shown good skin penetration after topical application. Therefore, in the present study the main focus was on the pathology, pathogenesis, and consequently topical treatment of candidiasis. Nanogel containing miconazole have been prepared from the natural polymers i.e. gelatin and chitosan. The nanogel of miconazole (100 mg) nitrate was formulated by modified emulsification-diffusion technique and characterized for different parameters. From all the seven nanogel formulations named as F1 to F7, F1 (Gelatin and Chitosan in the percentage of 82.85 and 17.15 respectively) have been selected as model formulations. The reason behind that was as per ICH stability guideline, the formulations F1 was found optimum and stable. Miconazole nanogel formulations F1 also showed the maximum release i.e. 78 % approximately. XRD showed the formulated nanogel was in crystalline shape. In summary, the miconazole nanogel drug delivery systems have two main advantages i.e. they are topical preparation as well as nano sized. It can be postulated that nanogel may be a best approach to treat the fungal skin diseases.

Vicissitudes in polyphenolic extract-based high internal phase creams (HIPCs)- effect of storage temperature dependent characteristics.

The purpose of this investigation was to evaluate the vicissitudes in polyphenolic extract- based high internal phase creams (HIPCs) and effect of storage temperature dependent characteristics. Rheological parameters, that is, power law and IPC analysis with its physical characteristics were exploredat different storage temperatures (8°, 25°, 40° and 40° with 75% relative humidity- RH) with different time intervals up to 2 months of newly formulated poly-phenolic extract- based high internal phase cream and its comparison with base. Polyphenolic- based HIPCs showed non-Newtonian-pseudo plastic tendencies in vicissitudes with time and storage temperatures. Data analysis with Power Law and IPC paste was found to fit to all the rheograms. Flow index, shear sensitivity factor, consistency Index and 10 RPM of freshly prepared HIPCs with and without encapsulated polyphenolic extract were found to be 0.5,0.53, 386.4 cP, and 432.9 cP, respectively.The viscosities were fallen with rise in shear stress.There was no change in color, electrical conductivity, liquefaction and phase separation after centrifugation in any sample of polyphenolic extract-based HIPCs and its base. Polyphenolic- based extract HIPCs behaved non-Newtonian- pseudo plastic tendencies and showed stability up to 2 months and can be directed absolutely to shield skin against ultraviolet radiation (UV) intervened oxidative mutilation.

Effect of varying quantities of polymer on preparation and stability evaluation of carbamazepine cocrystals with dicarboxylic acid coformers.

The current study is an attempt to explore the effect of varying quantities of hydroxypropyl cellulose (HPC) polymer on carbamazepine (CBZ) cocrystal formation with dicarboxylic acid coformers i.e., malonic acid (MA), succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The cocrystals were first prepared without polymer by slurry crystallization method and then tried with different quantities of the polymer. The prepared samples were characterized by Powder X-ray Diffraction (XRPD). The characterization results indicate that in methanol pure carbamazepine-malonic (CBZ-MA) and carbamazepine-adipic acid (CBZ-AA) cocrystal can be prepared, while in ethanol and acetone pure carbamazepine-succinic (CBZ-SA) and carbamazepine-glutaric acid (CBZ-GA) cocrystals can be obtained respectively. The same cocrystals were tried using HPC polymer in three different quantities. The characterization results showed that a higher quantity of HPC polymer transforms CBZ-MA cocrystal polymorph-I to polymorph-II. The CBZ-SA and CBZ-GA cocrystal formation somehow inhibited as the concentration of HPC polymer increases. But on the other side, the formation of CBZ-AA cocrystal utterly not inhibited in the presence of varying quantities of HPC polymer. Furthermore, 11 different quantities of HPC were tried to know about the inhibitory concentration of HPC on CBZ-AA cocrystal formation. The CBZ-AA cocrystal preparation was not inhibited even at higher quantities of HPC compared to the coformer. Additionally, the effect of three different quantities of HPC on the thermal stability of the CBZ-AA cocrystal was investigated. Moreover, the stability of pure CBZ at 92% relative humidity (RH) condition was compared to CBZ-AA cocrystal with and without HPC polymer. The CBZ-AA cocrystal with and without HPC polymer was more stable than pure CBZ.

Phytochemical, antimicrobial and time-kill kinetics potentials of Euphorbia nivulia Buch.-Ham.: A Cholistan desert medicinal plant.

Euphorbia nivulia a locally occurring plant species possesses antiseptic, analgesic and anti-inflammatory properties and is ethnopharmacologically used in various ailments like skin, ear disorders, boils, and worm infestation. Preliminary phytochemical screening showed presence of flavonoids, polyphenolics, glycosides, alkaloids, tannins and triterpenoids in (70% aqueous-ethanolic) Euphorbia nivulia crude extract (En cr) and its four fractions, i.e., hexane fraction (En hex), butanol fraction (En bt), chloroform fraction (En ch), and aqueous fraction (En aq). In current study, Agar well diffusion and time-kill kinetic assays were performed for antimicrobial activity. 300 mg/ml concentration showed maximum inhibitory zone. Highest zone of inhibition (15.5mm) was demonstrated by En ch fraction against Proteus mirabilis. Staphyllococcus aureus was the most sensitive bacteria against whom all fractions except En aq fraction were active. Maximum MIC (15.3 mg/ml) was shown by En ch fraction against Proteus mirabilis. Similarly, En ch fraction showed (15.1 mg/ml) remarkable MIC against Candida albicans. Significant higher antibacterial and antifungal activity was revealed in high concentration. Time-kill kinetics studies revealed bacteriostatic action. Noteworthy antimicrobial activity may be due to bioactive compounds of extract which may be a potential antibacterial and antifungal agent.