Muhammed Majeed

Ascorbic Acid and Tannins from Emblica officinalis Gaertn. Fruits—A Revisit

The fruits of Emblica officinalis Gaertn. (Euphorbiaceae), also known as amla in Ayurveda, are considered to be a rich source of ascorbic acid. However, the antioxidant activities exhibited by E. officinalis extract are superior to those of ascorbic acid itself. Low molecular hydrolyzable tannins emblicanins A and B have been suggested in the earlier literature to be the contributory antioxidant molecules in the extract. This work finds no evidence for the presence of emblicanins A and B in the extract. In addition, the high content of ascorbic acid is also questionable due to previous nonidentification of coeluting mucic acid gallates. This paper reports a new HPLC method to detect even trace amounts of ascorbic acid in E. officinalis fruit juice or extract.

Targeting beta-Catenin signaling to induce apoptosis in human breast cancer cells by z-Guggulsterone and Gugulipid extract of Ayurvedic medicine plant Commiphora mukul

Backgroundz-Guggulsterone (z-Gug) and Gugulipid (GL) have been used to treat a variety of ailments. We now report their anti-cancer effect and mechanism against human breast cancer.MethodsUsing the human estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells as well as the normal human mammary epithelial cell line (HMEC), we evaluated the anti-breast-cancer efficacy and apoptosis inducing activity of GL. We determined the cellular and molecular mechanism of GL-inhibited breast cancer cell growth.ResultsGL significantly inhibited growth of MCF-7 and MDA-MB-231 cells with an IC50~2 μM at pharmacologically relevant concentrations standardized to its major active constituent z-Gug. The GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and caspase 3 activity. The GL-induced apoptosis was associated with down-regulation of the β-Catenin signaling pathway. The decreased expression of Wnt/β-Catenin targeting genes, such as cyclin D1, C-myc and survivin, and the inhibition of the activity of the transcription factor (T-cell factor 4, TCF-4) were observed in GL-treated breast cancer cells. The GL treatment resulted in a significant reduction of β-Catenin /TCF-4 complex in both of the cancer cells. The GL-induced apoptotic cell death was significantly enhanced by RNA Interference of β-Catenin and TCF-4. On the other hand, the normal human mammary epithelial cell HMEC, compared with the human breast cancer cells, is significantly more resistant to growth inhibition and apoptosis induction by GL.ConclusionThe present study indicates that the β-Catenin signaling pathway is the target for GL-induced growth inhibition and apoptosis in human breast cancer.

Bacillus coagulans MTCC 5856 supplementation in the management of diarrhea predominant Irritable Bowel Syndrome: a double blind randomized placebo controlled pilot clinical study

BackgroundBacillus coagulans MTCC 5856 has been marketed as a dietary ingredient, but its efficacy in diarrhea predominant irritable bowel syndrome (IBS) condition has not been clinically elucidated till date. Thus, a double blind placebo controlled multi-centered trial was planned to evaluate the safety and efficacy of B. coagulans MTCC 5856 in diarrhea predominant IBS patients.MethodsThirty six newly diagnosed diarrhea predominant IBS patients were enrolled in three clinical centres. Along with standard care of treatment, 18 patients in group one received placebo while in group two 18 patients received B. coagulans MTCC 5856 tablet containing 2u2009×u2009109xa0cfu/day as active for 90xa0days. Clinical symptoms of IBS were considered as primary end point measures and were evaluated through questionnaires. The visual analog scale (VAS) was used for abdominal pain. Physician’s global assessment and IBS quality of life were considered as secondary efficacy measures and were monitored through questionnaires.ResultsLaboratory parameters, anthropometric and vital signs were within the normal clinical range during the 90xa0days of supplementation in placebo and B. coagulans MTCC 5856 group. There was a significant decrease in the clinical symptoms like bloating, vomiting, diarrhea, abdominal pain and stool frequency in a patient group receiving B. coagulans MTCC 5856 when compared to placebo group (pu2009<u20090.01). Similarly, disease severity also decreased and the quality of life increased in the patient group receiving B. coagulans MTCC 5856 when compared to placebo group.ConclusionsThe study concluded that the B. coagulans MTCC 5856 at a dose of 2u2009×u2009109xa0cfu/day along with standard care of treatment was found to be safe and effective in diarrhea predominant IBS patients for 90xa0days of supplementation. Hence, B. coagulans MTCC 5856 could be a potential agent in the management of diarrhea predominant IBS patients.

Evaluation of genetic and phenotypic consistency of Bacillus coagulans MTCC 5856: a commercial probiotic strain.

Commercial probiotics preparation containing Bacillus coagulans have been sold in the market for several decades. Due to its high intra-species genomic diversity, it is very likely that B. coagulans strain may alter in different ways over multiple years of production. Therefore, the present study focuses to evaluate the genetic consistency and probiotic potential of B. coagulans MTCC 5856. Phenotypic and genotypic techniques including biochemical profiling, 16S rRNA sequencing, GTG 5″, BOX PCR fingerprinting, and Multi-Locus-Sequence typing (MLST) were carried out to evaluate the identity and consistency of the B. coagulans MTCC 5856. Further, in vitro probiotic potential, safety and stability at ambient temperature conditions of B. coagulans MTCC 5856 were evaluated. All the samples were identified as B. coagulans by biochemical profiling and 16S rRNA sequencing. GTG 5″, BOX PCR fingerprints and MLST studies revealed that the same strain was present over 3xa0years of commercial production. B. coagulans MTCC 5856 showed resistance to gastric acid, bile salt and exhibited antimicrobial activity in in-vitro studies. Additionally, B. coagulans MTCC 5856 was found to be non-mutagenic, non-cytotoxic, negative for enterotoxin genes and stable at ambient temperature (25xa0±xa02xa0°C) for 36xa0months. The data of the study verified that the same strain of B. coagulans MTCC 5856 was present in commercial preparation over multiple years of production.

Synthesis and Evaluation of the Anti-Oxidant Capacity of Curcumin Glucuronides, the Major Curcumin Metabolites

Curcumin metabolites namely curcumin monoglucuronide and curcumin diglucuronide were synthesized using an alternative synthetic approach. The anti-oxidant potential of these curcumin glucuronides was compared with that of curcumin using DPPH scavenging method and Oxygen Radical Absorbance Capacity (ORAC) assay. The results show that curcumin monoglucuronide exhibits 10 fold less anti-oxidant activity (DPPH method) and the anti-oxidant capacity of curcumin diglucuronide is highly attenuated compared to the anti-oxidant activity of curcumin.

Efficacy and safety of 1% forskolin eye drops in open angle glaucoma - An open label study.

Purpose Current treatment for glaucoma includes beta-blockers and prostaglandin analogues which have their own disadvantages. Thus a need exists for new ocular hypotensive agents that are more efficacious and have fewer side effects. Therefore, forskolin eye drops 1%, through herbal product; a clinical trial was carried out for the safety and efficacy in the treatment of open angle glaucoma. Methods Ninety adult male/female patients of 18–60 years of age, of either sex, suffering from open angle glaucoma with an intraocular pressure (IOP) of more than 24 mm Hg were enrolled in the study. Patients were advised to instill 2 drops thrice a day (8:00 h, 14:00 h and 20:00 h) and tonometric readings were recorded on baseline visit and on Visit 2, i.e. end of 1st week, Visit 3–2nd week, Visit 4–3rd week, and Visit 5–4th week. The reduction in IOP across each time point from untreated baseline visit and reduction in IOP across various study visits were measured. Results The mean (95% CI) difference in reduction in IOP was 4.5 mm Hg (P < 0.05) in the right eye and was 5.4 mm Hg (p < 0.05) in the left eye from baseline visit (Visit 1) to final visit (Visit 5). Conclusions Forskolin 1% eye drops can be a safe alternative to beta blockers in glaucoma patients having concomitant asthma.

Disparate Effects of Stilbenoid Polyphenols on Hypertrophic Cardiomyocytes In Vitro vs. in the Spontaneously Hypertensive Heart Failure Rat

Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,4′-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects of gnetol (trans-3,5,2′,6′-tetrahydroxystilbene) and pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene) on cardiac hypertrophy. In vitro, gnetol and pterostilbene prevented endothelin-1-induced indicators of cardiomyocyte hypertrophy including cell enlargement and protein synthesis. Gnetol and pterostilbene stimulated AMP-activated protein kinase (AMPK), and inhibition of AMPK, using compound C or shRNA knockdown, abolished these anti-hypertrophic effects. In contrast, resveratrol, gnetol, nor pterostilbene reduced blood pressure or hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat. In fact, AMPK levels were similar between Sprague-Dawley and SHHF rats whether treated by stilbenoids or not. These data suggest that the anti-hypertrophic actions of resveratrol (and other stilbenoids?) do not extend to the SHHF rat, which models heart failure superimposed on hypertension. Notably, SHHF rat hearts exhibited prolonged isovolumic relaxation time (an indicator of diastolic dysfunction), and this was improved by stilbenoid treatment. In conclusion, stilbenoid-based treatment as a viable strategy to prevent pathological cardiac hypertrophy, a major risk factor for heart failure, may be context-dependent and requires further study.

A Double-Blind, Placebo-Controlled, Parallel Study Evaluating the Safety ofBacillus coagulans MTCC 5856 in Healthy Individuals

Objective: LactoSpore® containing probiotic strain Bacillus coagulans MTCC 5856 has been marketed as a dietary ingredient for nearly two decades. Clinical data on the safety and tolerance has not been evaluated at a dose of 2×109 cfu (spores)/day in healthy individuals. Thus, the primary objective of this study was to investigate the safety and tolerability of B. coagulans MTCC 5856 in healthy adults. Study design: A total of 40 participants were randomized into one of two groups in a double-blind, randomized, placebo-controlled parallel study. One group of participants (n=20) were administered B. coagulans MTCC 5856 (600 mg tablet), containing 2×109 cfu (spores). The control group (n=20) was administered placebo tablets. Safety and tolerability of B. coagulans MTCC 5856 was assessed over 30 days by safety laboratory parameters (blood hematology and clinical chemistry parameters), anthropometric measures (weight, BMI, blood pressure and heart rate), adverse events, Bristol stool score, tolerability questionnaire and bowel habit diary. Results: All laboratory parameters, anthropometric and vital sign measures remained within normal clinical range during the 30 day supplementation. Similar adverse events (AE’s) were reported by participants in both the placebo and the B. coagulans MTCC 5856 group. The number of bowel movements and the Bristol stool scores were similar between the placebo group and B. coagulans MTCC 5856 group during the 30 days of supplementation. Participants also reported that B. coagulans MTCC 5856 tablets were tolerable and easy to swallow. Conclusions: This study has verified that B. coagulans MTCC 5856 at a dose of 2 × 109 cfu (spores)/day was safe and tolerable in healthy participants when supplemented for 30 days.

Calebin A: Analytical Development for Pharmacokinetics Study, Elucidation of Pharmacological Activities and Content Analysis of Natural Health Products

PURPOSEnTo develop a bioanalytical assay using RP-HPLC to quantify the curcuminoid calebin A, to characterize its pharmacokinetics in rats after intravenous (IV) and oral (PO) administration, to identify its pharmacological activities and to evaluate its content in natural health products.nnnMETHODSnAn RP-HPLC method was developed for the detection of calebin A. Separation was carried out using a Phenomenex® Kinetex® C18 column with UV detection at 339 nm. An isocratic mobile phase consisting of acetonitrile and water with 10 mM ammonium formate (pH 7.0) (40:60, v/v) at a flow rate of 0.8 mL/min was employed. Linear standard curves were established and applied in the pharmacokinetic study. Calebin A was administered to male Sprague-Dawley (CD) rats IV (20 mg/kg) or PO (500 mg/kg) (n=4/route of administration). Serum and urine samples were collected for 72 h post dose. In vitro antioxidant activity, anti-inflammatory activity (cyclooxygenase and lipoxygenase inhibition), dipeptidyl peptidase-4 (DPP-4) inhibition and cytochrome P450 inhibitory activties of calebin A were examined using commercial assay kits. Content analysis of calebin A in 14 natural health products advertised to contain turmeric were carried out using methanolic extraction.nnnRESULTSnThe HPLC method was successfully applied to a pharmacokinetic study of calebin A in rats. After IV and PO administration of calebin A, the compound was detected as the aglycone and a glucuronidated metabolite. Oral bioavailabitily was found to be ~0.5%, serum half-life was ~1-3 h. Calebin A appears to be primarily excreted via non-renal routes. Calebin A possessed concentration-dependent antioxidant activity and DPP-4 inhibition. Calebin A appears to be a non-selective cyclooxygenase inhibitor and also a poor lipoxygenase inhibitor. The curcuminoid displayed in vitro interactions with CYP2D6 and CYP1A2. Content analysis of 14 natural health products that claimed to contain turmeric showed that concentration of calebin A was inconsistent among the products.nnnCONCLUSIONnA successful assay was developed for the detection of calebin A using RP-HPLC. Preliminary pharmacokinetic studies indicate that an unoptimised formulation of calebin A has poor oral bioavailability. Calebin A exhibits various pharmacological activities. This article is open to POST-PUBLICATION REVIEW. Registered readers (see For Readers) may comment by clicking on ABSTRACT on the issues contents page.

Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism.