Efficacy of green jackfruit flour as a medical nutrition therapy replacing rice or wheat in patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study.

BACKGROUND/OBJECTIVES: Medical nutrition therapy along with pharmacological interventions as a multidisciplinary approach is required to treat type 2 diabetes mellitus (T2DM). This study evaluated the efficacy of Jackfruit365™ green jackfruit flour as an integral part of daily meal in patients with T2DM. SUBJECTS/METHODS: This was a randomized, double-blind, placebo-controlled study conducted between May 2019 and February 2020. Patients of either sex aged ≥18 to ≤60 years with a diagnosis of T2DM for >1 year receiving oral antihyperglycemic agents were randomized (1:1) to receive either jackfruit flour 30 g/day (Group A) or placebo flour (Group B) (breakfast and dinner) daily for 12 weeks replacing an equal volume of rice or wheat flour. The primary endpoint was a mean change in glycosylated hemoglobin (HbA1c). Other endpoints were mean changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), lipid profile, and body weight. The independent t-test was used to compare changes between the groups. RESULTS: A total of 40 patients were enrolled (n = 20 each). A significantly higher reduction in HbA1c was observed in Group A compared to Group B from baseline to week 12 [-2.73 mmol/mol (-0.25%) vs. 0.22 mmol/mol (0.02%), p = 0.006]. The mean change in FPG and PPG was significantly higher in Group A than that of Group B (p = 0.043 and p = 0.001). The continuous glucose monitoring showed decreasing mean blood glucose in 7 days of administration of jackfruit flour meal. CONCLUSION: Patients from Group A had a significantly higher reduction in HbA1c, FPG, and PPG than Group B demonstrating the efficacy of jackfruit flour in glycemic control as medical nutrition therapy replacing an equal volume of rice or wheat flour in daily meal. CLINICAL TRIAL REGISTRY: CTRI/2019/05/019417.

Microbial production of omega-3 fatty acids: an overview.

The essence of appropriate nutritional intake on a regular basis has a great impact in maintaining fundamental physiological functions and the body metabolism. Considering how pivotal maintaining a nourishing fat diet is to human health, Omega-3 fatty acids have gained a lot of attention in recent times. Omega-3 fatty acids (n-3 FAs) such as eicosapentaenoic acid (EPA) and DHA are considered as essential fatty acids (EFAs) offering enormous nutritional benefits: from playing a major role in the prevention and treatment of a number of human diseases, such as cardiovascular disorders and neurological disorders, to having anti-inflammatory properties, to providing joint support, etc. Hence, their incorporation into our daily diet is of great importance. Also, both EPA and DHA have been shown to be therapeutically significant in treating several infectious diseases. EFAs were initially thought to be marine in origin, produced by fishes. Consequentially, this led to the increase in the industrial extraction of fish oils for meeting the commercial need for of n-3-rich dietary supplements. Although fish oil supplementation met almost all of the dietary demand for EFAs, they did come with a fair share of drawbacks such as undesirable odour and flavour, heavy metal contamination, extinction of fish species, etc. Oleaginous micro-organisms are a promising alternative for the production of a more sustainable, consistent and quality production of n-3 FAs. Thus, the entire review focuses on understanding the eco-friendlier production of n-3 FAs by micro-organisms.

A comprehensive review on ethnomedicine, phytochemistry, pharmacology, and toxicity of Tephrosia purpurea (L.) Pers.

Tephrosia purpurea (L.) Pers. is a well-known plant in Ayurveda and named "Sarwa wranvishapaka" for its property to heal wounds. Traditionally, it is practiced for impotency, asthma, dyspepsia, hemorrhoids, syphilis gonorrhea, rheumatism, enlargement of kidney and spleen. It is an important component of herbal preparations like Tephroli and Yakrifti used to cure liver disorders. Various phytocompounds including pongamol, purpurin, purpurenone, tephrosin, bulnesol, tephrostachin, ß-sitosterol, and so on have been reported. Modern pharmacological studies have shown that the plant have wound healing, antileishmanial, anticarcinogenic, antimicrobial, antioxidant, hepatoprotective, antifertility, antispermatogenic, anti-diarrheal, diuretic, and insecticidal properties. Acetylcholinesterase inhibitory action reported from this plant aids its utilization for the development of drugs for Alzheimer's and dementia neurological disorders. Among the known active compounds of T. purpurea, tephrostachin is responsible for antiplasmodial activity, tephrosin, pongaglabol, and semiglabrin exerts antiulcer activity while quercetin, rutin, ß-sitosterol, and lupeol are mainly responsible for its anti-inflammatory and anti-cancer properties. From different toxicological studies, concentrations up to 2,000 mg/kg were considered safe. The present review comprehensively summarizes the ethnomedicine, phytochemistry, pharmacology, and toxicology of T. purpurea. Further research on elucidation of the structure-function relationship among active compounds, understanding of multi-target network pharmacology and clinical applications will intensify its therapeutic potential.

Qualitative elemental analysis of selected potential anti-asthmatic medicinal plant taxa using EDXRF technique.

Qualitative elemental analysis was determined in various parts of potential anti-asthmatic medicinal plants using Energy Dispersive X-ray Fluorescence (EDXRF) spectrometer. X-ray beam was used to excite each sample and spectra were recorded with a high resolution Si(Li) detector. The data analysis was carried out by the nEXT software. Trace elements P, S, Cl, K, Ca, Mn, Fe, Cu, Zn, Se, Br, Rb and Sr were estimated and elemental concentrations were determined. The results of the present study compared with standard reference material NIST1515 apple leaves for accuracy. The elements K, Ca, Cl, S and P are major constituents and besides Cu, Zn, Fe, Mn, Se, Br, Rb and Sr were present at low level. The presence of Cu, Zn, Mn and Se in medicinal plants plays a vital role on management and control of asthma disease.

A randomised placebo controlled clinical trial on the efficacy of Caralluma fimbriata supplement for reducing anxiety and stress in healthy adults over eight weeks.

BACKGROUND: This study investigated the efficacy of a succulent, Caralluma fimbriata extract (CFE) in reducing anxiety and stress in healthy adults. METHODS: An 8 week double-blind randomised clinical trial, in which 97 adults self-reporting mild to moderate anxiety were given 500 mg b.d. CFE (n = 49), or 500 mg b.d. placebo (n = 48). Anxiety and stress were measured at baseline, week 4, and week 8 to investigate the timing of treatment effect using the GAD-7, Perceived Stress Scale (PSS), Positive and Negative Affect Schedule (PANAS), and salivary cortisol. Data were analysed using mixed ANOVAs on SPSS v.24. RESULTS: Results indicated a significant reduction in anxiety and stress in both groups at week 4 and week 8. The reduction in the CFE group was significantly greater (p < .05) than in the placebo group on the GAD-7 and PSS at week 4 and week 8, and in Negative affect at week 4. Improvement in Positive affect was greater in the CFE group than in the placebo group at week 8. Cortisol analysis indicated that CFE may act through the Hypothalamic-Pituitary-Adrenal (HPA) axis, showing statistically significant changes in males, but not in females. LIMITATIONS: Self-reported instruments involve subjective interpretation thus salivary cortisol was employed as a more objective measure. The study would benefit from a larger sample and longer trial, and the inclusion of a wait-list group to allow comparison between treatment and no treatment. CONCLUSIONS: The findings indicate that CFE is superior to placebo in reducing subclinical anxiety and stress over 8 weeks.

Formulation and evaluation of ileo-colonic targeted matrix-mini-tablets of Naproxen for chronotherapeutic treatment of rheumatoid arthritis.

In this present research work, the aim was to develop ileo-colonic targeted matrix-mini-tablets-filled capsule system of Naproxen for chronotherapeutic treatment of Rheumatoid Arthritis. So Matrix-mini-tablets of Naproxen were prepared using microsomal enzyme dependent and pH-sensitive polymers by direct compression method which were further filled into an empty HPMC capsule. The compatibility was assessed using FT-IR and DSC studies for pure drug, polymers and their physical mixtures. The prepared batches were subjected to physicochemical studies, drug content estimation, in-vitro drug release and stability studies. When FTIR and DSC studies were performed, it was found that there was no interaction between Naproxen and polymers used. The physicochemical properties of all the prepared matrix-mini-tablets batches were found to be in limits. The drug content percentage in the optimized formulation F18 was found to be 99.24 ± 0.10%. Our optimized matrix-mini-tablets-filled-capsule formulation F18 releases Naproxen after a lag time of 2.45 ± 0.97 h and 27.30 ± 0.86%, 92.59 ± 0.47%, 99.38 ± 0.69% at the end of 5, 8, 12 h respectively. This formulation was also found to be stable as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. Thus, a novel ileo-colonic targeted delivery system of Naproxen was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis.

Aquifer wise seasonal variations and spatial distribution of major ions with focus on fluoride contamination-Pandharkawada block, Yavatmal district, Maharashtra, India.

Seasonal variations in groundwater reveal lesser concentrations of major ions except NO3(-) during post-monsoon seasons in shallow aquifers as compared to deeper aquifers. The F(-) concentration from deeper aquifers is high in both seasons and shows a moderate positive relationship with weathering depth and is >5 mg/L in compound lava flow. Groundwater is mainly a Ca-HCO3 type in shallow aquifers and mixed type in deeper aquifers. Fluoride shows a positive correlation with pH, Na(+), HCO3(-) in shallow aquifers and an inverse correlation with Ca(2+) and HCO3(-) from deeper aquifers in both seasons. Approximately 45% of the samples are not suitable for drinking from both aquifers but suitable for irrigation purposes. Rock-water interaction, moderate alkalinity, sluggish movement, and higher residence time are the main causes for high F(-) in deeper aquifers as compared to shallow aquifers. As recommendations, drinking water requirement may be met from shallow aquifers/surface water and fluoride rich groundwater for other purposes. Most effective defluoridation techniques like ion exchange and reverse osmosis may be adopted along with integrated fluorosis mitigation measures and rooftop rainwater harvesting. Supplementary calcium and phosphorous rich food should be provided to children and creating awareness about safe drinking water habits, side effects of high F(-), and NO3(-) rich groundwater, improving oral hygiene conditions are other measures.

Neonatal exposure to 17ß-estradiol down-regulates the expression of synaptogenesis related genes in selected brain regions of adult female rats.

AIMS: Administration of estradiol or compounds with estrogenic activity to newborn female rats results in irreversible masculinization as well as defeminization in the brain and the animals exhibit altered reproductive behavior as adults. The cellular and molecular mechanism involved in inducing the irreversible changes is largely unknown. In the present study, we have monitored the changes in the expression of selected synaptogenesis related genes in the sexually dimorphic brain regions such as POA, hypothalamus and pituitary following 17ß-estradiol administration to neonatal female rats. MAIN METHODS: Female Wistar rats which were administered 17ß-estradiol on day 2 and 3 after birth were sacrificed 120days later and the expression levels of genes implicated in synaptogenesis were monitored by semi-quantitative reverse transcription PCR. Since estradiol induced up-regulation of COX-2 in POA is a marker for estradiol induced masculinization as well as defeminization, in the present study only animals in which the increase in expression of COX-2 gene was observed in POA were included in the study. KEY FINDINGS: Down-regulation of genes such as NMDA-2B, NETRIN-1, BDNF, MT-5 MMP and TNF-α was observed in the pre-optic area of neonatally E2 treated female rat brain but not in hypothalamus and pituitary compared to the vehicle- treated controls as assessed by RT-PCR and Western blot analysis. SIGNIFICANCE: Our results suggest a possibility that down-regulation of genes associated with synaptogenesis in POA, may be resulting in disruption of the cyclical regulation of hormone secretion by pituitary the consequence of which could be infertility and altered reproductive behavior.

Polypyrimidine tract-binding proteins of potato mediate tuberization through an interaction with StBEL5 RNA.

Polypyrimidine tract-binding (PTB) proteins are a family of RNA-binding proteins that function in a wide range of RNA metabolic processes by binding to motifs rich in uracils and cytosines. A PTB protein of pumpkin was identified as the core protein of an RNA-protein complex that trafficks RNA. The biological function of the PTB-RNA complex, however, has not been demonstrated. In potato, six PTB proteins have been identified, and two, designated StPTB1 and StPTB6, are similar to the phloem-mobile pumpkin type. RNA binding assays confirmed the interaction of StPTB1 and StPTB6 with discrete pyrimidine-rich sequences of the 3'-untranslated regions of the phloem-mobile mRNA, StBEL5. The promoter of StPTB1 was active in companion cells of phloem in both stem and petioles. Expression of both types was evident in phloem cells of roots and in stolons during tuber formation. RNA accumulation of both PTB proteins was induced by short days in leaves in correlation with enhanced accumulation of StBEL5 RNA. StPTB suppression lines exhibited reduced tuber yields and decreased StBEL5 RNA accumulation, whereas StPTB overexpression lines displayed an increase in tuber production correlated with the enhanced production in stolons of steady-state levels of StBEL5 transcripts and RNA of key tuber identity genes. In StPTB overexpression lines, both the stability and long-distance transport of StBEL5 transcripts were enhanced, whereas in suppression lines stability and transport decreased. Using a transgenic approach, it is shown that the StPTB family of RNA-binding proteins regulate specific stages of development through an interaction with phloem-mobile transcripts of StBEL5.

Lecithin-linker formulations for self-emulsifying delivery of nutraceuticals.

Lecithin-linker microemulsions are formulations produced with soybean lecithin in combination with a highly lipophilic (lipophilic linker) and highly hydrophilic (hydrophilic linkers) surfactant-like additives. In this work, lecithin-linker systems were formulated to produce self-emulsifying delivery systems for ß-carotene and ß-sitosterol. The concentration of the lipophilic linker, sorbitan monooleate, was adjusted to minimize the formation of liquid crystals. The concentration of hydrophilic linkers, decaglyceryl caprylate/caprate and PEG-6-caprylic/capric glycerides, was gradually increased (scanned) until single phase clear microemulsions were obtained. For these scans, the oil (ethyl caprate) to water ratio was set to 1. The single phase, clear microemulsions were diluted with fed-state simulated intestinal fluid (FeSSIF) and produced stable emulsions, with drop sizes close to 200 nm. Using pseudo-ternary phase diagrams to evaluate the process of dilution of microemulsion preconcentrates (mixtures of oil, lecithin and linkers with little or no water) with FeSSIF, it was determined that self-emulsifying systems are obtained when the early stages of the dilution produce single phase microemulsions. If liquid crystals or multiple phase systems are obtained during those early stages, then the emulsification yields unstable emulsions with large drop sizes. An in vitro permeability study conducted using a Flow-Thru Dialyzer revealed that stable emulsions with drop sizes of 150-300 nm produce large and irreversible permeation of ß-carotene to sheep intestine. On the other hand, unstable emulsions produced without the linker combination separated in the dialyzer chamber.

Trace elemental distribution in the scalp hair of bipolars using PIXE technique.

Trace metals play a significant role in neurological disorders. There is very limited information available on the role of macro and trace elements in bipolar disorders. The objective of this investigation was to identification, quantification of essential trace elements in the scalp hair samples of the patients and compare with those of normal subjects. We made a hypothesis about the role played by essential trace metals whose concentrations are significantly different to those of normals in the disease process. The analysis was carried out in the scalp hair samples of 26 male and 26 female patients suffering from bipolar disorder (BD) by Particle Induced X-ray Emission Technique (PIXE). The concentration of Cu (p < 0.002) was found to be higher in the hair samples of male bipolar disorder patients while the concentrations of Mn (p < 0.001), Fe (p < 0.005), Zn (p < 0.0001) and Se (p < 0.005) were found to be lower than those in normal subjects. The concentration of Cu (p < 0.0001) was higher in the hair samples of female bipolar patients but depressed levels of Fe (p < 0.005), Ni (p < 0.05), Zn (p < 0.00001) and Se (p < 0.05) were observed compared to controls. Cu/Zn ratio was found to be higher in the hair samples of male and female patients compared with normals. While the imbalance of certain trace elements leads to generation of more free radicals, the imbalance of some other trace elements causes changes in dopamine (neurotransmitter) activity. It is essential to monitor before and periodically during treatment the levels of essential trace elements for effective treatment of bipolar disorder.

Mapping and characterization of the interaction interface between two polypyrimidine-tract binding proteins and a nova-type protein of Solanum tuberosum.

Polypyrimidine tract-binding (PTB) proteins are RNA-binding proteins that generally contain four RNA recognition motifs (RRMs). In potato, six cDNAs encoding full-length PTB proteins have been identified. In the present study Nova1-like protein, designated StNova1, was identified as a potential interacting partner of the StPTB proteins via yeast two-hybrid screening. Nova protein is a RNA-binding protein that contains three K-homology (KH) domains. In humans, these proteins are involved in regulation of neuronal RNA metabolism but the role of Nova-like proteins in plants is poorly understood. We have validated this interaction and mapped the protein binding region on StNova1 and StPTB1 and -6 using a novel domain interaction phage display (DIPP) technique. The interaction between the two RNA-binding proteins StPTB1/6 and StNova1 is mediated through linker regions that are distinctly separated from the RRMs. Furthermore, using a random 21-mer phage-peptide library, we have identified a number of peptides with the consensus sequence motif [S/G][V/I][L/V]G that recognize the StPTB proteins. One over-represented peptide that recognizes StPTB6 contains the GVLGPWP sequence that is similar to the GIGGRYP sequence in the glycine-rich linker region between the KH2 and KH3 domains of StNova1. We show, through site-specific mutations, the importance of glycine and proline residues in StNova1-StPTB interactions.

Cultivation of green alga Botryococcus braunii in raceway, circular ponds under outdoor conditions and its growth, hydrocarbon production.

The present study focused on cultivation, seasonal variation in growth, hydrocarbon production, fatty acids profiles of Botryococcus braunii (LB-572 and N-836) in raceway & circular ponds under outdoor conditions. After 18days of cultivation the biomass yield and hydrocarbon contents were increased in both raceway and circular ponds. The fat content was found to be around 24% (w/w) with palmitic and oleic acids as prominent fatty acids. Hydrocarbons of C(20)-C(30) carbon chain length were higher in raceway and circular ponds. Maximum biomass yield (2gL(-1)) and hydrocarbon content (28%) were observed in Nov-Dec. In case of B. braunii (N-836) after 25days of cultivation the biomass yield was 1gL(-1) and hydrocarbon content was 27%. Supplementation of 0.1% NaHCO(3) in the medium resulted in biomass yield of 1.5gL(-1) and hydrocarbon content of 30% compared to control.

Production of gymnemic acid depends on medium, explants, PGRs, color lights, temperature, photoperiod, and sucrose sources in batch culture of Gymnema sylvestre.

Gymnema sylvestre (R.Br.) is an important diabetic medicinal plant which yields pharmaceutically active compounds called gymnemic acid (GA). The present study describes callus induction and the subsequent batch culture optimization and GA quantification determined by linearity, precision, accuracy, and recovery. Best callus induction of GA was noticed in MS medium combined with 2,4-D (1.5 mg/L) and KN (0.5 mg/L). Evaluation and isolation of GA from the calluses derived from different plant parts, namely, leaf, stem and petioles have been done in the present case for the first time. Factors such as light, temperature, sucrose, and photoperiod were studied to observe their effect on GA production. Temperature conditions completely inhibited GA production. Out of the different sucrose concentrations tested, the highest yield (35.4 mg/g d.w) was found at 5% sucrose followed by 12 h photoperiod (26.86 mg/g d.w). Maximum GA production (58.28 mg/g d.w) was observed in blue light. The results showed that physical and chemical factors greatly influence the production of GA in callus cultures of G. sylvestre. The factors optimized for in vitro production of GA during the present study can successfully be employed for their large-scale production in bioreactors.

Chemoprotective influence of Zanthoxylum sps. on hepatic carcinogen metabolizing and antioxidant enzymes and skin papillomagenesis in murine model.

In the present study, the putative potential of pericarp of dried fruit of Zanthoxylum (Rutaceae Family), a common spice additive in India's west coast cuisines, in protecting against carcinogenesis has been reported. Extract from dried fruit of Zanthoxylum was orally administered to mice at two dose levels: 100 and 200 mg/kg body wt. for 14 days. Results reveal bifunctional nature of Zanthoxylum species as deduced from its potential to induce phase-I and phase-II enzyme activities associated with carcinogen activation and detoxification in the liver of mice. Hepatic glutathione S-transferase and DT-diaphorase were found significantly elevated by the treatment. Zanthoxylum was also effective in augmenting the antioxidant enzyme activities of glutathione peroxidase, superoxide dismutase and catalase albeit significantly by high dose of the extract (P < 0.05; P < 0.01). Reduced glutathione was also significantly elevated in the liver of treated animals (P < 0.05). The present study also investigated peri-initiation application of acetone extract of Zanthoxylum on initiated mouse skin. Results showed a significant reduction in tumor incidence from 68% to 36% (P < 0.05); as well as, a reduction in tumor burden per effective mouse from 3.87 to 0.72 (P < 0.01). Cumulatively, the findings strongly suggest cancer chemopreventive potential of Zanthoxylum sps.

Chemomodulatory potential of Glycine max against murine skin and cervical papillomagenesis.

In the present study, chemopreventive potential of Glycine max (G. Max) seeds was examined against DMBA-induced skin and MCA-induced cervical papillomagenesis in Swiss albino mice. Different doses (2.5, 5, and 7.5% w/w) of G. max were provided to animals in feed. Results exhibited a significant reduction in skin as well as cervical tumor incidence and tumor multiplicity (up to 75%) at all doses of test diet as compared to the control. Relatively, 7.5% test diet was most effective in protecting the animals against carcinogenesis. Further, detoxifying enzymes and antioxidative status was also evaluated in the liver of mice to understand the role of G. max in prevention of cancer. It was observed that the test diet containing G. max significantly elevated the specific activities of glutathione-S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD), catalase (CAT), and glyoxalase I (Gly I). The test diet also elevated the content of reduced glutathione whereas it decreased the level of the peroxidative damage along with the specific activity of lactate dehydrogenase. It appeared that G. max seeds provided chemoprevention against skin and cervical papillomagenesis probably by modulating the detoxifying and antioxidative enzymes. It could be inferred that intake of G. max might help in reducing the risk of cancer.

The effect of L-carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients.

Protein energy malnutrition and inflammation are common and usually concurrent in maintenance hemodialysis (MHD) patients. Carnitine, a small molecule involved in fatty acid metabolism, is significantly decreased in long-term HD patients. L-Carnitine supplementation may have potential benefits in improving dialysis-related disorders. However, there are conflicting reports with regard to the beneficial effects of L-Carnitine supplementation. Hence, the present study was carried out to evaluate the effect of L-Carnitine supplementation on lipid parameters, apoproteins and inflammatory and nutritional markers in HD patients. A total of 35 patients with end-stage renal disease, on MHD for a period of 2 to 5 years were recruited into the study. The study group consisted of 20 patients who received Carnitine supplementation intravenously three times a week after each HD session, at 1 g/dose, while the control group consisted of 15 patients without supplementation with L-Carnitine. Highly sensitive C-reactive protein (hsCRP), total protein, albumin, lipid profile and apoprotein AI and B were determined at baseline and at the end of the study. A significant decrease in the hsCRP levels was observed in the Carnitine-supplemented group (P < 0.05). However, no significant change was observed in the lipid parameters and nutritional markers in the Carnitine-supplemented group. In conclusion, the present study demonstrates the significant benefit of L-Carnitine supplementation on inflammatory status in MHD patients as noted by marked decrease in hsCRP levels in comparison with the control group.

Sorafenib and its tosylate salt: a multikinase inhibitor for treating cancer.

Sorafenib, a drug that targets malignant cancer cells and cuts off the blood supply feeding the tumour, has been crystallized as the free base, 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N-methylpyridine-2-carboxamide, C(21)H(16)ClF(3)N(4)O(3), (I), and as a tosylate salt, 4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl)pyridinium 4-methylbenzenesulfonate, C(21)H(17)ClF(3)N(4)O(3)(+)·C(7)H(7)O(3)S(-), (II). In both structures, the sorafenib molecule is in an extended conformation. The pyridine-2-carboxamide group exhibits a syn conformation of the N atoms in (I), whereas an almost anti orientation is present in (II). In both crystal structures, the two terminal groups, viz. pyridine-2-carboxamide and the trifluorophenyl ring, are oriented differently to the conformations found in enzyme-bound sorafenib. The sorafenib molecules in (I) are linked into zigzag chains by N-H···O hydrogen bonds, whereas in (II) the presence of the additional tosylate anion results in the formation of chains of fused hydrogen-bonded rings. This study reveals the variations in the solid-state conformation of the sorafenib molecule in different crystalline environments.

Interaction of sesamol (3,4-methylenedioxyphenol) with tyrosinase and its effect on melanin synthesis.

Sesamin, sesamolin (lignans) and sesamol--from sesame seed (Sesamum indicum L.)--are known for their health promoting properties. We examined the inhibition effect of sesamol, a phenolic degradation product of sesamolin, on the key enzyme in melanin synthesis, viz. tyrosinase, in vitro. Sesamol inhibits both diphenolase and monophenolase activities with midpoint concentrations of 1.9 µM and 3.2 µM, respectively. It is a competitive inhibitor of diphenolase activity with a K(i) of 0.57 µM and a non-competitive inhibitor of monophenolase activity with a K(i) of 1.4 µM. Sesamol inhibits melanin synthesis in mouse melanoma B16F10 cells in a concentration dependant manner with 63% decrease in cells exposed to 100 µg/mL sesamol. Apoptosis is induced by sesamol, limiting proliferation. This study of the chemistry and biology of lignans, in relation to the mode of action of bioactive components, may open the door for drug applications targeting enzymes.

Supplementation with the antioxidant lycopene significantly decreases oxidative stress parameters and the bone resorption marker N-telopeptide of type I collagen in postmenopausal women.

UNLABELLED: To date, no intervention studies have been published demonstrating the effect of the antioxidant lycopene on bone. Postmenopausal women supplemented with lycopene had significantly increased antioxidant capacity and decreased oxidative stress and the bone resorption marker N-telopeptide (NTx). Lycopene decreases bone resorption markers and may reduce the risk of osteoporosis. INTRODUCTION: We have previously shown in vitro and in vivo that lycopene from tomato is associated with a protective effect on bone, but lycopene intervention studies have not been reported. Our aim was to carry out a randomized controlled intervention study to determine whether lycopene would act as an antioxidant to decrease oxidative stress parameters, resulting in decreased bone turnover markers, thus reducing the risk of osteoporosis in postmenopausal women. METHODS: Sixty postmenopausal women, 50-60 years old, were recruited. Following a 1-month washout without lycopene consumption, participants consumed either (N = 15/group): (1) regular tomato juice, (2) lycopene-rich tomato juice, (3) tomato Lyc-O-Mato lycopene capsules, or (4) placebo capsules, twice daily for total lycopene intakes of 30, 70, 30, and 0 mg/day respectively for 4 months. Serum collected after the washout, 2 and 4 months of supplementation, was assayed for cross-linked aminoterminal N-telopeptide, carotenoid content, total antioxidant capacity (TAC), lipid, and protein oxidation. RESULTS: Participants who consumed juice or lycopene capsules were analyzed in one group designated "LYCOPENE-supplemented". Repeated measures ANOVA showed that LYCOPENE-supplementation for 4 months significantly increased serum lycopene compared to placebo (p < 0.001). LYCOPENE-supplementation for 4 months resulted in significantly increased TAC (p < 0.05) and decreased lipid peroxidation (p < 0.001), protein oxidation (p < 0.001), and NTx (p < 0.001). These decreases in lipid peroxidation, protein oxidation, and NTx were significantly different from the corresponding changes resulting from placebo supplementation (p < 0.05, p < 0.005, and p < 0.02, respectively). CONCLUSIONS: Our findings suggest that the antioxidant lycopene is beneficial in reducing oxidative stress parameters and the bone resorption marker NTx.