Combination therapy with Hordeum vulgare, Elettaria cardamomum, and Cicer arietinum exhibited anti-diabetic potential through modulation of oxidative stress and proinflammatory cytokines.

Poly-herbal therapies for chronic diseases like diabetes mellitus (DM) have been practiced in south Asia for centuries. One of such therapies comprises of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum that have shown encouraging therapeutic potential in the treatment of diabetes and obesity. Therefore, poly-herbal granules (PHGs) of this formula were developed and investigated for their anti-diabetic and anti-obesity potential in obese-diabetic rats. The developed PHGs were chemical characterized and the virtual molecular docking was performed by Discovery studio visualizer (DSV) software. For in-vivo experiment, obesity in rats was induced with high-fat high-sugar diet. After that, diabetes was induced by alloxan monohydrate 150 mg/kg i.p. injection. The diseased rats were treated with PHGs at 250, 500 and 750 mg/kg/day for four weeks. GC-MS analysis of PHGs demonstrated the presence of 1,3-Benzenedicarboxylic acid bis(2-ethylhexyl) ester and 1,2-Benzenedicarboxylic acid di-isooctyl ester and phenol, 2,4-bis(1,1-dimethylethyl). Molecular docking of these compounds demonstrated higher binding energies with receptor than metformin against α-amylase and α-glucosidase. PHGs exhibited a decline in body weight, HbA1c, hyperlipidemia, hyperglycemia, and insulin resistance in diseased rats. The histopathological examination revealed that PHGs improved the alloxan-induced damage to the pancreas. Furthermore, PHGs increased the SOD, CAT and GSH while and the decreased the level of MDA in the liver, kidney and pancreas of diseased rats. Additionally, the PHGs had significantly downregulated the TNF-α and NF-κB while upregulated the expression of NrF-2. The current study demonstrated that the PHGs exhibited anti-diabetic and anti-obesity potential through amelioration of oxidative stress, NF-κB, TNF-α, and NrF-2 due to the presence of different phytochemicals.

Anxiolytic interventions of extracts and pure compounds from Adenanthera pavonina and Peltophorum pterocarpum leaves to treat acute anxiety and depression symptoms in mice.

Anxiolytic effect of ethanol, hexane extracts and pure compounds ß- sito sterol glucoside and bergenin isolated from Adenanthera pavonina AP (Fabaceae) and Peltophorum pterocarpum PP (Fabaceae) leaves were monitored in this study. Mice were treated with dose of 125mg/kg body weight of ethanol and hexane leaves extracts of both tested plants while, 5mg/kg body weight of ß-sito sterol glucoside and 25mg/kg body weight of bergenin. The effect was monitored by hole board test, forced swimming test, open field apparatus and stationary rod test. Results from neuropharmacological effects revealed that ethanol extract of AP leaves and hexane extract of PP leaves had significant anxiolytic (forced swimming test) exploratory (head dip and open field test) and neuro activator activity (stationary rod test) at tested dose. The greatest anti-depressant and anxiolytic effect was found in ethanol extract of AP leaves when compared to all treated drugs. A part from memory enhancing effects, diazepam treated mice also exhibited anxiolytic and antidepressant effects and found comparable with ethanol extract of AP. These findings may clarify the impact of ethanol, hexane extracts and pure substances ß-sitosterol glucoside and bergenin at tested concentrations, as well as their potential to treat the Parkinson's and related disorders as an alternative therapy.

Chemical characterization, antioxidant and antidiabetic activities of a novel polyherbal formulation comprising of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum extracts.

Diabetes mellitus (DM) is the most prevalent endocrine disorder. Numerous individual herbs possess anti-diabetic activity. The seeds of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum are traditionally used to manage DM. The ambition of this work was to formulate the poly-herbal granules (PHGs) comprising of these three functional foods and evaluate their in-vitro antioxidant and antidiabetic potential. The dried seed extracts of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum were used in a ratio of 2.5:1:1 to formulate PHGs by wet granulation method. The ratio of extracts was selected on the basis of traditional phytotherapies popularly used by local Hakeems of Pakistan to achieve glycemic control in diabetic patients resistant to traditional allopathic regime of medicine. The flow properties of developed PHGs were evaluated. The UV-Visible spectroscopic, Fourier Transform Infrared (FTIR) and HPLC-DAD of all seed extracts and PHGs were performed. The in-vitro antioxidant DPPH, FRAP, total antioxidant capacity (TAC) and Nitric Oxide (NO) scavenging assays were carried out on PHGs. The in-vitro antidiabetic activity of PHGs was investigated by alpha-amylase and alpha-glucosidase enzyme inhibition activity. The developed PHGs exhibited excellent flow properties. The UV-Vis spectra of all seed extracts and PHGs demonstrated peak at 278 nm showing the presence of flavonoids and phenols. The FTIR spectra confirmed the existence of flavonoids, and phenols along with amines in seed extracts as well as PHGs. The HPLC-DAD test revealed the existence of gallic acid, ascorbic acid, Quercetin-3-(caffeoyldiglucoside)-7-glucoside, Rosmarinic acid, delphinidin-3,5-diglucosides, Kaempferol-3-feruloylsophoroside-7-glucoside and Phloroglucinol in PHGs. The PHGs exhibited IC50 of 51.23, 58.57, 55.41 and 53.13 µg/mL in DPPH assay, FRAP assay, TAC, Nitric oxide scavenging assays respectively. The PHGs also demonstrated IC50 of 49.97 and 36.16 µg/mL in alpha-amylase and in alpha-glucosidase inhibition assays respectively in dose dependent manner. The developed PHGs exhibited an excellent flow property. These exhibit significant in-vitro antioxidant and antidiabetic profile by virtue of flavonoid and phenolic acid derivatives.

SeDeM expert system with I-optimal mixture design for oral multiparticulate drug delivery: An encapsulated floating minitablets of loxoprofen Na and its in silico physiologically based pharmacokinetic modeling.

Introduction: A SeDeM expert tool-driven I-optimal mixture design has been used to develop a directly compressible multiparticulate based extended release minitablets for gastro-retentive drug delivery systems using loxoprofen sodium as a model drug. Methods: Powder blends were subjected to stress drug-excipient compatibility studies using FTIR, thermogravimetric analysis, and DSC. SeDeM diagram expert tool was utilized to assess the suitability of the drug and excipients for direct compression. The formulations were designed using an I-optimal mixture design with proportions of methocel K100M, ethocel 10P and NaHCO3 as variables. Powder was compressed into minitablets and encapsulated. After physicochemical evaluation lag-time, floating time, and drug release were studied. Heckel analysis for yield pressure and accelerated stability studies were performed as per ICH guidelines. The in silico PBPK Advanced Compartmental and Transit model of GastroPlus™ was used for predicting in vivo pharmacokinetic parameters. Results: Drug release follows first-order kinetics with fickian diffusion as the main mechanism for most of the formulations; however, a few formulations followed anomalous transport as the mechanism of drug release. The in-silico-based pharmacokinetic revealed relative bioavailability of 97.0%. Discussion: SeDeM expert system effectively used in QbD based development of encapsulated multiparticulates for once daily administration of loxoprofen sodium having predictable in-vivo bioavailability.

SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™.

The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK "ACAT" model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r 2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.

Formulation and evaluation of natural antitussive cough syrups.

Among respiratory complications, cough is an important defensive pulmonary reflex that removes fluids, irritants or foreign substances from the respiratory tract. Rosa damascene Mill, petal extract is a traditional medicine and reported to use in the management of cough. In the present study rose petals extract samples were used to prepare natural antitussive cough syrups containing ivy leaf extract to observe synergistic effect of rose water in managing coughing in rats. Four cough formulations (A1, A2, A3 and A4) were prepared. The antitussive activity was observed at three dosage levels; 5ml, 10ml and 15ml. Cough was induced by the standard procedure using sulfur dioxide gas and ammonia. The antitussive activity was recorded by observing the coughing bouts. The result indicated that all formulations had a good effect on cough reduction at 90min but comparing the effect of formulations in all doses formulations, A2 followed by A3 and A4 at 30 minute time interval which is good in comparison with standard Diphenhydramine HCL and Dextromethorphan HBr 10ml in sulfur dioxide gas and ammonia induced cough. Hence, the results of the present study indicated the synergistic effect of rose water in the management of cough ailments.

The mechanistic insight of polyphenols in calcium oxalate urolithiasis mitigation.

About 12% of world population is affected by different forms of urolithiasis of which the recurrence rate in female is 47-60% and in male is 70-80%. Standard therapeutic agents (allopurinol, citrate, cystone and thiazide diuretics) are used to prevent and treat urolithiasis but these are not universally-effective due to common kidney stone relapse and other side effects. Surgical treatment causes long-term renal damage, hypertension and stone recurrence. Polyphenols, the plant-derived bioactive molecules, have showed protection against cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases, among a number of other ailments. The role of these phytochemicals in urolithiasis management is emerging. Hence, the present review discusses peer-reviewed published literature till date on this aspect and highlights that polyphenols could effectively inhibit the formation of calcium oxalate urinary stones (most common renal stone), correlating with their antioxidant, anti-inflammatory, diuretic and angiotensin-converting enzyme (ACE) inhibition. Further, we have proposed the prospects and challenges in developing the plant polyphenols into drugs against kidney stone prevention. This review might be a stepping stone for further investigation into the clinical implications of the polyphenols in urolithiasis remediation.

Essential minerals and phytic acid in legumes with reference to their nutritive and medicinal properties.

Three commonly used legumes, Macrotyloma uniflorum (Lam.) Verdc., Phaseolus lunatus Linn., and Phaseolus vulgaris Linn., were subjected to determine their minerals and phytic acid contents to correlate their nutritional and medicinal properties. To quantify essential minerals, atomic absorption spectroscopic method, while for phytic acid estimation, spectrophotometric method was used. Presence of Fe, Mg, Mn, P and Zn were recorded in good quantities, Ca and Cu in moderate, while K in small quantity in the seed flours of all the three tested legumes. Maximum Fe and Zn content (0.38 and 0.40 mg/g) were recorded in P. vulgaris, while M. uniflorum delivered high content of Mg, Mn, P and Ca (0.21, 0.20, 77.94 and 0.04 mg/g) and 0.04 mg/g Cu was recorded in P. lunatus. The highest level of phytic acid (37.00 mg/g) was recorded in M. uniflorum at 519 nm. The estimated quantities of minerals and phytic acid provide a good opportunity to draw a conclusion that all the three tested legumes could potentially be used as food to achieve nutritional and health related functional benefits.

Growth patterns of monosodium urate monohydrate (gouty and urinary) crystals in gel: An in vitro study.

Monosodium urate monohydrate crystals are deposited in peripheral joints causing gout and elicit an intense localized inflammatory attack whereas in collecting ducts and medullary interstitium as a urinary calculi which causes dysuria, nausea and hematuria. The purpose of present study is to observe possible growth patterns of monosodium urate monohydrate crystals. The crystals were grown in test tubes by single diffusion gel technique and were observed at 7th, 14th, 21st, 28th and 40th day. Needle and spherulite type crystals were observed at 14th day, while arboresque, crystal sheaves, densely branched, dumbbell, mushroom type spherulites, plumose and hexagonal prismatic crystals were observed for the first time. After 40th day complete spherulites were observed with their aggregates. The crystals were characterized by Scanning Electron Microscopy, Energy-Dispersive X-ray and Fourier Transform infra Red spectroscopies. The pattern of MSUM will be helpful to determine the role of different natural products in the modulation, inhibition or promotion of these crystals by affecting the shape, size, transparency, approximate number and total mass of growing crystals. In case of inhibition or modulation it will be helpful for evaluation the prophylactic management whereas the promotion of the crystal will give an idea about the risk factors of gout and kidney stones.

Review: Antiurolithiatic plants: Formulations used in different countries and cultures.

About 12% of world population is affected by different forms of urolithiasis in which the recurrence rate in female is 47-60% and in male is 70-80%. According to WHO 75% people rely on traditional medicines for the prevention and cure of different ailments. Similarly, the majority of the world population use a number of plants to treat problems related to the urinary tract system in which urolithiasis is the major cause. The aim of the review is to collect the data of the plants used in different parts and cultures of the world against urolithiasis with their parts, mode of preparation, dosage and administration. A literature review was conducted for traditionally used antiurolithiatic plants. The articles mentioning plant, parts, mode of preparation, dose and route of administration were selected. This information was extracted to compose Mono and Poly herbal antiurolithiatic formulations used in Appalachia (region in Eastern United States), Canada, India, Iran, Israel, Italy, Jordan, Latin America, Pakistan, Turkey and Yemen. The review provides an important data about plants used as antiurolithiatic in different parts of the world. The information not only useful for common people, but also for the scientific community to carry out further phytochemical, pharmacological and toxicological studies for the discovery of new, effective and safer molecules against urolithiasis.

Analgesic and anti-inflammatory activities of Piper nigrum L.

OBJECTIVE: To evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats. METHODS: The analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats. RESULTS: Piperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P<0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in writhing test, ethanol extract significantly (P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatory effect using plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min. CONCLUSIONS: It is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities.

Formulation design and evaluation of Cefuroxime axetil 125 mg immediate release tablets using different concentration of sodium lauryl sulphate as solubility enhancer

Cefuroxime axetil immediate release tablets were formulated by direct compression method with different percentages of sodium lauryl sulphate (SLS) such as 0.5, 1.0, 1.5 and also without SLS. Resulting batches of tablets were evaluated by both pharmacopeial and non-pharmacopeial methods to ascertain the physico-mechanical properties. Dissolution test were carried out in different medium like 0.07 M HCl, distilled water, 0.1M HCl of pH 1.2 and phosphate buffers at pH 4.5 and 6.8 to observe the drug release against the respective concentration of SLS used. Later, test formulations were compared by f1 (dissimilarity) and f2 (similarity) factors using a reference brand of cefuroxime axetil. Significant differences (p<0.05) in dissolution rate were recorded with the change in concentration of SLS in different media. Test formulation T3 containing 1% SLS was found to be best optimized formulation based on assay, disintegration, dissolution and similarity and dissimilarity factors.

Formularam-se comprimidos de liberação imediata à base de cefuroxima axetil, pelo método de compressão direta, com diferentes percentagens de lauril sulfato de sódio (LSS), tais como 0,5, 1,0, 1,5, e também sem SLS. Os lotes resultantes dos comprimidos foram avaliados por ambos os métodos da farmacopeia e não farmacopeicos para determinar as propriedades físico-mecânicas. O teste de dissolução foi realizado em meios diferentes, como HCl 0,07 M, água destilada, HCl 0,1 M com pH 1,2 e os tampões fosfato (pH 4,5 e 6,8) para observar a liberação do fármaco contra a correspondente concentração de LSS utilizado. Em seguida, as formulações de teste foram comparadas por fatores f1 (dissimilaridade) e f2 (similaridade), utilizando uma marca de referência de cefuroxima axetil. Diferenças significativas (p<0,05) na taxa de dissolução foram registradas com a mudança na concentração de LSS em diferentes meios de dissolução. A formulação T3 contendo LSS a 1% foi considerada a melhor formulação otimizada com base nos ensaios de desintegração, dissolução e fatores de semelhança e dissimilaridade.

Bioactive alkaloids produced by fungi. I. Updates on alkaloids from the species of the genera Boletus, Fusarium and psilocybe.

Fungi, in particular, are able in common with the higher plants and bacteria, to produce metabolites, including alkaloids. Alkaloids, along with other metabolites are the most important fungal metabolites from pharmaceutical and industrial point of view. Based on this observation, the authors of this review article have tried to provide an information on the alkaloids produced by the species of genera: Boletus, Fusarium and Psilocybef from 1981-2009. Thus the review would be helpful and provides valuable information for the researchers of the same field.

Studies on the chemical composition of kohl stone by X-ray diffractometer.

Use of Kohl (Surma) creates toxicity or protects eye, is one of the most controversial topic of modern medicines. However, modern researches show that kohl forms a thin film on the eye lens thus avoiding the direct contract of harmful UV radiation and glare of sun with lens. Black and shining particles of galena in kohl shield the eyes from glare and reflection of sun and thus protect them from harmful effect of UV radiation emerging from the sun. Based on these findings and other properties of kohl, it was decided to undertake this study to ascertain it's chemical composition and to correlate these properties scientifically. In the present study, kohl stone obtained from Madina (Saudi Arabia) was analyzed to ascertain it's chemical composition. The chemical analysis and X-ray diffractometer results obtained, showed that the main component of kohl stone is galena (PbS).

Herbal treatment for cardiovascular disease the evidence based therapy.

More than 2000 plants have been listed in the Traditional (Herbal/Alternative) systems of medicine and some of these are providing comprehensive relief to the people suffering from cardio-vascular diseases, specially "hyperlipidemia" and "ischemic heart disease". WHO reports indicate that around eighty percent of the global population still relies on botanical drugs and several herbal medicines have advanced to clinical use in modern times. Based on these findings, present review is written to identify the "Pharmacology and Cardio-vascular Application" of four commonly used plants in Pakistan. These include, Crataegus oxycantha, Inula racemosa, Terminalia arjuna and Commiphora mukul. The selection of the plants in the present study is primarily based on their chemistry and pharmacological properties including toxicology reported in various research articles and reviews. Some very interesting findings have been observed and thus recorded and reported in this review.

Kohl (surma): retrospect and prospect.

Kohl, since antiquity has always been given a prime importance in ophthalmology for the protection and treatment of various eye ailments. However, for decades various conflicting reports in the literature have been published relating to Kohl application to eyes being responsible for causing higher blood lead concentration, which may cause lead poisoning. While at the same time, a number of research studies and reports have also been published negating any such links with increased blood lead level upon Kohl (surma) application. In view of the above mentioned facts, this review article is written with the objective to highlight various data from past and present research studies and reports about Kohl, so as to provide valuable information to both the users and the research workers about it's scientific background and effects when applied into eyes. A large number of items and topics (such as Kohl, surma, eye cosmetic, traditional eye preparations, environmental lead pollution, galena, lead sulphide etc.) have been taken into consideration while compiling this review article. In conclusion, the authors of this review article feel that the relation between Kohl and toxicity or increased blood lead concentration upon it's application to eyes as reported elsewhere is likely to be more of theoretical nature rather than a practical health hazard.