Evaluation of Acute Toxicity of Some Medicinal Plants and their Combination in Albino Mice

Medicinal plants find use across different cultures in the world. People have derived numerous benefits by using various plants for centuries. Herbal drugs are supposed to be safe, but there are chances these might cause toxicity and other complications. Thus toxicity studies are essential for a medicinal plant before being used in humans. The present research revolves around studying the acute toxicity of Ocimum kilimandscharicum, Thymus serpyllum, Spilanthes acmella and their combination in equal ratio (COMB). For preparing the combination of extracts, the ethanolic extracts of the three plants were combined in equal amounts and administered to the animals. The acute toxicity study was carried out according to OECD (The Organisation for Economic Co-operation and Development) guideline 423 for acute toxicity. The animals were divided into four groups each containing three animals each. These groups were respectively administered ethanolic extract of O. kilimandscharicum, T. serpyllum, S. acmella and COMB in a dose of 2000 mg/kg. The animals were observed for signs of toxicity and mortality at durations specified by OECD. The results demonstrated that extracts of the three medicinal plants used in the study and their combination were found to be safe up to 2000 mg/kg

FABRICATION AND CHARACTERIZATION OF RALOXIFENE LOADED SOLID-LIPID NANOPARTICLES

Objective:  The poor water solubility of the drug presents a great challenge for the formulation development and results in low oral bioavailability. The oral bioavailability of Raloxifene HCl (RLX) is very low (<2%) in humans due to its poor solubility. The objective of the present study was to develop RLX loaded solid-liquid nanoparticles for effective drug delivery. Methods: Compritol 888 ATO-based RLX-loaded solid lipid nanoparticles (SLNs) were formulated using the oil in water microemulsion method. Drug-excipients compatibility was confirmed through Fourier transform infrared spectroscopy, Differential scanning calorimetry methods. The SLN was characterized for particle size, surface morphology, entrapment efficiency. Results: A total of seventeen formulations (SLN1-SLN17) were developed as per the 3 levels 3 factor Box–Behnken design. The model used for the analysis was statistically analyzed using ANOVA and the goodness of fit was evaluated using diagnostic plots. As per the response-surface plots, the amount of lipid, poloxamer 407, and ultrasonication time have a significant effect on the particle size and entrapment efficiency (%EE). The developed RLX-loaded SLNs have the size and %EE in the range of 165.63±2.62 nm to 315.33±4.87 nm and 75.21±2.32% to 95.32±2.11%. The TEM analysis showed that the developed RLX-loaded SLNs were almost spherical and has a small size range. Conclusion: The high biocompatibility, biodegradability, ability to protect drugs in GIT, and sustained release properties make SLNs an ideal candidate to resolve poor oral bioavailability challenges

Programmed delivery of verapamil hydrochloride from tablet in a capsule device

O objetivo do presente trabalho foi desenvolver sistema de liberação programada de cloridrato de verapamil capaz de liberação imediata do fármaco após 6 h de intervalo de tempo usando polímeros hidrofílicos. O corpo da cápsula foi impermeabilizado por tratamento de vapor de formaldeído, enquanto a tampa não foi submetida ao tratamento. Dois comprimidos foram inseridos na cápsula (comprimidos em cápsula) seguido de mistura de bicarbonato de sódio: ácido cítrico e lactose, utilizados como excipientes. O alginato de sódio, a quitosana, o HPMC K15 e o complexo quitosana:alginato de sódio foram utilizados para modular a razão de liberação do fármaco. A combinação entre o HPMC K15 e o ajuste da proporção do complexo quitosana:alginato de sódio permitiu a liberação do fármaco após 6 h. O efeito dos excipientes na liberação do fármaco foi também avaliado. Verificou-se que o tempo de latência foi reduzido na presença de maior quantidade de lactose, enquanto o menor tempo foi observado empregando maior concentração da mistura efervescente.The aim of the present work was to develop a programmed drug delivery system which would be able to release the drug after 6 h of lag time by use of hydrophilic polymers. The capsule body was made impermeable by use of formaldehyde vapor treatment, while the cap was untreated. The capsule was filled with two layered tablets (tablet-in-capsule), followed by a sodium bicarbonate:citric acid mixture (SBCM) and lactose as bulking agent. Sodium alginate, chitosan, HPMC K15 and chitosan:sodium alginate complex (CSAC) were used as the rate modulating layer. Through combined use of HPMC K15 and adjusting the ratio of CSAC, the desired lag time of 6 h was obtained. The effect of the bulking agents on the lag time were also studied and it was found that the lag time was decreased with higher amounts of lactose, and delayed dissolution and decreased lag time was observed at higher amount of effervescent mixture

FORMULATION, OPTIMIZATION, AND EVALUATION OF IN-SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE FOR OPHTHALMIC DRUG DELIVERY

Objective: The present study emphasizes the synthesis, optimization, and evaluation of ocular in-situ gel for ophthalmic drug delivery against conjunctivitis. Methods: Pre-formulation studies on the drug and polymers were carried out, which included the study of various physicochemical properties of the drug and drug-polymer compatibility studies. The 12 different formulations were further pre-optimised by Taguchi method for determining the number of influential factors. Furthermore, the formulation optimization was done by using ‘Box–Behnken’ design (BBD) (Design expert 10 software) for assessing the effect of formulation variables on product characteristics viz. viscosity, gelation temperature (GT), and mean release time (MRT). About 13 suggested runs of the experiment were carried out and formulations were optimised. Finally, three batches of the optimised formulation were prepared and evaluated for in vitro drug release, isotonicity of formulation, anti-microbial potential, ocular irritancy, and accelerated stability testing. Results: Pre-formulation study confirmed the purity, solubility, and compatibility of drug measured by λmax, partition coefficient, stability study, and Fourier-transform infrared spectroscopy (FTIR) analysis. Taguchi screening method suggested about 12 different formulations and 3 most prominent influential factors including viscosity, GT, and drug release. 13 different formulations designed based on ‘BBD’ method were further optimised by considering the most influential factors suggested by Taguchi screening. The in vitro evaluation of the optimised formulation gave satisfactory results in terms of drug release, and anti-microbial activity. It was found to be isotonic with no ocular irritancy. Further, the preparation immediately transformed from sol to gel upon administration into cul-de-sac region of the eye due to multi-dimensional approaches utilised for in-situ gel formation namely temperature change Pluronic, ion sensitivity due to Gellan-gum, pH sensitivity because of Carbopol. Conclusion: The optimised in-situ gelling ocular drug formulation showed promising potency for ophthalmic drug delivery with no irritancy due to the multifactorial mechanism

FORMULATION AND OPTIMIZATION OF THERMOSENSITIVE IN-SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE FOR OCULAR DRUG DELIVERY

Objective: The present study has focused on development and optimization of thermosensitive in-situ ocular drug delivery system for the treatment of conjunctivitis.Methods: Thermosensitive in-situ hydrogel formulation of moxifloxacin hydrochloride was developed by dispensing variable concentration of pluronic F-127, gellan-gum, and carbopol in distilled water. Viscosity, gelation temperature and mean release time (MRT) were measured by using ‘Brookfield' viscometer LV-III (spindle no. 40), rheological techniques and dissolution apparatus respectively. Optimization for ideal formulation was carried by ‘Box–Behnken' design on the basis of prime factors of the formulation including viscosity, gelation temperature, and MRT. Moreover, the optimized formulation was evaluated for accelerated stability study by in vitro drug release, anti-microbial potential by ‘Kirby-Bauer disk diffusion' method and ocular irritancy assay were done by in vivo analysis.Results: Optimised thermosensitive in-situ gel, when administered into cul-de-sac region of the eye, it was immediately transformed from sol to gel by multi-dimensional mechanism due to plurionic, gellan-gum, carbopol. The optimized formulation minimizes the chances of formulation failure as well as the concentration on individual polymer which dependence on a single mechanism of gelation. The final optimised formulation consists of plurionic (11.50% w/v), gellan-gum (0.32% w/v), carbopol (0.3% w/v), shows optimum therapeutic effect. Moreover, the accelerated stability study, anti-microbial potential, and ocular irritancy confirmed the biocompatibility of optimized in-situ drug-containing gel with high potency and stability.Conclusion: Thus, optimized in-situ drug-containing gel with multifactorial approaches showed promising ocular formulation having minimum side effect and high therapeutic efficacy.Â

Treatment with Green Tea Prevents Intracerebroventricular Streptozotocin Induced Cognitive Impairment and Oxidative Stress in Mice

Green tea polyphenols have demonstrated significant antioxidant, anti-carcinogenic, anti-mutagenic and antidiabetic in numerous human, animal and in vitro studies. Hence present study was design to evaluate the influence of green tea in streptozotocin induced oxidative stress in mice.Morris water maze, Elevated plus maze and passive avoidance apparatus was used for the evaluation of learning and memory. Brain thiobarbituric acid reactive substance was also estimated.Intracerebroventricular administration of streptozotocin reduces the learning and memory and increase the concentration of thiobarbituric acid reactive substance in mice. Green tea significantly improves the learning and memory and reverses the increase thiobarbituric acid reactive substance concentration in mice.The result of present study indicates that green tea improve the learning and memory. It also reduces the streptozotocin induced oxidative stress.Keyword: Hippocampus, degenerative disease, green te

Treatment with Green Tea Prevents Intracerebroventricular Streptozotocin Induced Cognitive Impairment and Oxidative Stress in Mice

Green tea polyphenols have demonstrated significant antioxidant, anti-carcinogenic, anti-mutagenic and antidiabetic in numerous human, animal and in vitro studies. Hence present study was design to evaluate the influence of green tea in streptozotocin induced oxidative stress in mice.Morris water maze, Elevated plus maze and passive avoidance apparatus was used for the evaluation of learning and memory. Brain thiobarbituric acid reactive substance was also estimated.Intracerebroventricular administration of streptozotocin reduces the learning and memory and increase the concentration of thiobarbituric acid reactive substance in mice. Green tea significantly improves the learning and memory and reverses the increase thiobarbituric acid reactive substance concentration in mice.The result of present study indicates that green tea improve the learning and memory. It also reduces the streptozotocin induced oxidative stress.Keyword: Hippocampus, degenerative disease, green te

ANTIOXIDANT ACTIVITY OF ETHANOLIC EXTRACT OF OCIMUM KILIMANDSCHARICUM USING HYDROXYL RADICAL SCAVENGING METHOD

In our modern society, we are constantly being challenged by numerous diseases. The majority of these diseases are as a result of the stressful and unhealthy lifestyle that has been adopted by modern man. Due to the polluted environment, unhealthy lifestyles and fast food culture there is the overproduction of reactive oxygen and nitrogen species in a human body. These reactive oxygen and nitrogen species have become the most important culprits for the development of neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, aging and many other diseases. Newer findings in the etiology of various diseases have implicated free radicals and oxidative species in the development of various diseases. So, to find the newer treatments of various diseases we should deeply research the area of antioxidants. Nature has provided us with various medicinal plants which contain phytochemicals that have potent antioxidant potentials. Himalayan herbs have been known since time immemorial to cure even uncurable diseases. The current study focuses on the antioxidant potential of ethanolic extract of aerial parts of Ocimum kilimandscharicum at very low concentrations using hydroxyl radical scavenging activity. This study aims to unravel the potentials of truly potent herbs in the field of antioxidants, which in future can provide cure to several diseases. Keywords: antioxidants, free radicals, Ocimum kilimandscharicum.Â

In Vitro Antiproliferative Efficacy, Antioxidant Activity and LC MS Based Metabolite Profiling of Premna Barbata Stem Bark

Premna barbata Wall. ex Schauer is used traditionally as folkloric medicines for the treatment of differentpathological conditions. The first reported constituent from the bark of the plant was an iridoid glycoside premnosidic acid having antioxidant activity. Other species of this genus i.e., Premna latifolia, Premna tomentosa has shown to have antioxidant and cytotoxic activities. Despite the ethnomedicinal uses, no scientific evidence in support of antitumor activity on the stem bark of Premna barbata is reported so far. Hence, the current work aims to assess anticancer potentiality of different extracts of P. barbata on various cancer cell lines. Different extracts i.e., Petroleum ether extract (PBPE), Chloroform extract (PBCE), Ethyl acetate extract (PBEE) and Alcoholic extract (PBAE) were prepared and on each extract in-vitro antiproliferative activity was performed by using SRB assay. The most potent extract i.e., PBEE was then evaluated for antioxidant activity. Qualitative phytochemical investigation of different extracts indicates the presence of proteins, carbohydrates, steroids/triterpenoids, alkaloids, glycosides, flavonoids, and phenolic constituents. Ethyl acetate extract of Premna barbata gives potent cytotoxic activity in all cancer cell lines but more selectively to human colon cancer cell line (COLO-205) with GI 50 44.6 μg/ml. The phenolic and flavonoid content in ethyl acetate extract was 3.43±0.09 mg GE/g and 4.28±0.18mg QE/g respectively. Nineteen compounds were observed in positive (+) ESI mode chromatograms when LC-MS analysis was carried out. The LC-MS analysis by positive ionization mode, the predicted compounds such as Geniposidic acid (synonym: Premnosidic acid) and Rutin were detected. The cytotoxicity observed on cancerous cell lines in our study may be due to the presence of observed compounds. So, it can be concluded that Premna barbata stembark has remarkable cytotoxic activity against different tumor cell lines but the effect is more on colon cell lines as compared to others

Hypoglycemic activity of aqueous extract of Urtica parviflora roxb. in normoglycemic rats

In the present study aqueous and ethanolic extract of leaves of Urtica parviflora were evaluated for hypoglycemic effect in normal rats using both 18 hr fasted rat model and oral glucose tolerance test. The aqueous extract of leaves showed a good hypoglycemic response in both the models, while ethanolic extract exhibited very week but insignificant effect, only in 18 hr fasted rat model. The aqueous extract was further tested for effect on intestinal glucose absorption. The amount of glucose absorbed in a segment of jejunum in situ was 13±0.75 mg in presence of aqueous extract vs. vs. 9.05±0.68 mg in control rats during 2 h (P<0.05). Phytochemical screening of aqueous extract revealed the presence of alkaloids, reducing sugars, polysaccharides, tannins, saponins, glycosides and flavonoids. The results indicate that aqueous extract possess significant hypoglycemic activity which may be attributed to, in part by reduction of intestinal glucose absorption by the abovementioned chemical constituents.Keywords: Hypoglycemic activity, Urtica parviflora, Oral glucose tolerance tes