From Gut to Hormones: Unraveling the Role of Gut Microbiota in (Phyto)Estrogen Modulation in Health and Disease.

The human gut microbiota regulates estrogen metabolism through the "estrobolome," the collection of bacterial genes that encode enzymes like ß-glucuronidases and ß-glucosidases. These enzymes deconjugate and reactivate estrogen, influencing circulating levels. The estrobolome mediates the enterohepatic circulation and bioavailability of estrogen. Alterations in gut microbiota composition and estrobolome function have been associated with estrogen-related diseases like breast cancer, enometrial cancer, and polycystic ovarian syndrome (PCOS). This is likely due to dysregulated estrogen signaling partly contributed by the microbial impacts on estrogen metabolism. Dietary phytoestrogens also undergo bacterial metabolism into active metabolites like equol, which binds estrogen receptors and exhibits higher estrogenic potency than its precursor daidzein. However, the ability to produce equol varies across populations, depending on the presence of specific gut microbes. Characterizing the estrobolome and equol-producing genes across populations can provide microbiome-based biomarkers. Further research is needed to investigate specific components of the estrobolome, phytoestrogen-microbiota interactions, and mechanisms linking dysbiosis to estrogen-related pathology. However, current evidence suggests that the gut microbiota is an integral regulator of estrogen status with clinical relevance to women's health and hormonal disorders.

Development and content validation of yoga module for the mental health of NICU mothers.

BACKGROUND: Postnatal yoga has been found to be effective for maternal mental health management. But a validated yoga module for the mental health of early postpartum mothers with infants admitted to the Neonatal Intensive Care Unit (NICU) is lacking. AIM: To design and validate a yoga module for the mental health of early postpartum mothers having infants admitted to the NICU. MATERIALS AND METHODS: First phase: A yoga module was designed through a review of published research articles and yogic texts for NICU mothers. Second phase: thirty-eight yoga experts validated the yoga module. Lawshe's formula was used to calculate each item's content validity ratio (CVR). The intra-class correlation coefficient was determined for the validated yoga module. Third phase: The validated yoga module was pilot-tested with a sample size of 20 NICU mothers. RESULTS: Thirty-eight yoga experts validated the yoga module for NICU mothers. Thirteen practices included in the module indicated good content validity (cutoff value: 0.316). The module's content validity index (CVI) and intra-class correlation coefficient were 0.672 and 0.924, respectively. Ten days of practicing the yoga module resulted in a significant reduction in maternal stress levels in the yoga group (p < 0.001) compared to the control group (p = 0.427). CONCLUSION: The present study suggests good content validity of the yoga module for the mental health of NICU mothers. However, future randomized controlled trials must be carried out to determine both the feasibility and clinical efficacy of the Yoga Module for NICU mothers.

Effects of umbilical cord milking versus delayed cord clamping on systemic blood flow in intrauterine growth-restricted neonates: A randomized controlled trial.

Recommendations for umbilical cord management in intrauterine growth-restricted (IUGR) neonates are lacking. The present randomized controlled trial compared hemodynamic effects of umbilical cord milking (UCM) with delayed cord clamping (DCC) in IUGR neonates > 28 weeks of gestation, not requiring resuscitation. One hundred seventy IUGR neonates were randomly allocated to intact UCM (4 times squeezing of 20 cm intact cord; n = 85) or DCC (cord clamping after 60 s; n = 85) immediately after delivery. The primary outcome variable was superior vena cava (SVC) blood flow at 24 ± 2 h. Secondary outcomes assessed were anterior cerebral artery (ACA) and superior mesenteric artery (SMA) blood flow indices, right ventricular output (RVO), regional cerebral oxygen saturation (CrSO2) and venous hematocrit at 24 ± 2 h, peak total serum bilirubin (TSB), incidences of in-hospital complications, need and duration of respiratory support, and hospital stay. SVC flow was significantly higher in UCM compared to DCC (111.95 ± 33.54 and 99.49 ± 31.96 mL/kg/min, in UCM and DCC groups, respectively; p < 0.05). RVO and ACA/SMA blood flow indices were comparable whereas CrSO2 was significantly higher in UCM group. Incidences of polycythemia and jaundice requiring phototherapy were similar despite significantly higher venous hematocrit and peak TSB in UCM group. The need for non-invasive respiratory support was significantly higher in UCM group though the need and duration of mechanical ventilation and other outcomes were comparable. CONCLUSIONS:  UCM significantly increases SVC flow, venous hematocrit, and CrSO2 compared to DCC in IUGR neonates without any difference in other hemodynamic parameters and incidences of polycythemia and jaundice requiring phototherapy; however, the need for non-invasive respiratory support was higher with UCM. TRIAL REGISTRATION: Clinical trial registry of India (CTRI/2021/03/031864). WHAT IS KNOWN: • Umbilical cord milking (UCM) increases superior vena cava blood flow (SVC flow) and hematocrit without increasing the risk of symptomatic polycythemia and jaundice requiring phototherapy in preterm neonates compared to delayed cord clamping (DCC). • An association between UCM and intraventricular hemorrhage in preterm neonates < 28 weeks of gestation is still being investigated. WHAT IS NEW: • Placental transfusion by UCM compared to DCC increases SVC flow, regional cerebral oxygenation, and hematocrit without increasing the incidence of symptomatic polycythemia and jaundice requiring phototherapy in intrauterine growth-restricted neonates. • UCM also increases the need for non-invasive respiratory support compared to DCC.

Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial.

Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate.   Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia.   Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.

Serum Calcium and Melatonin Levels in Neonates Undergoing Phototherapy.

Phototherapy-induced hypocalcemia has been postulated to result from a decline in serum melatonin levels. The present observational study evaluated the effects of phototherapy on serum calcium and melatonin levels, and assessed their correlation, if any. Eighty-nine neonates with a total serum bilirubin levels of 14.1 ± 2.8 mg/dL were recruited at the mean age of 51.9 ± 21.7 h. After a median interquartile range (IQR) duration of phototherapy for 24.0 (24-25.5) h, serum calcium levels decreased significantly, from 9.6 ± 0.8 to 9.4 ± 0.6 mg/dL; p = 0.02, leading to asymptomatic hypocalcemia in 2.2% of the neonates. Median (IQR) serum melatonin levels also decreased from 187.8 (133.5-227.6) to 176.3 (145.6-202.5) pg/mL after phototherapy, the difference being statistically insignificant. No significant correlation was documented between the duration of phototherapy with calcium and melatonin levels. The authors conclude that phototherapy resulted in a small but significant reduction of serum calcium levels without any significant correlation with serum melatonin.

Effects of delayed cord clamping in intrauterine growth-restricted neonates: a randomized controlled trial.

The time of cord clamping in intrauterine growth-restricted (IUGR) neonates remains an area of uncertainty. This assessor-blinded randomized controlled trial compared the effects of delayed cord clamping (DCC) with early cord clamping (ECC) on the systemic blood flow (SBF) and cerebral hemodynamics in IUGR neonates of gestational age ≥28 weeks, not requiring resuscitation. Eligible newborns were randomized to DCC (cord clamping after 60 s; n=55) or ECC (cord clamping within 30 s; n=55) group immediately after delivery. The primary outcome variable was superior vena cava (SVC) blood flow at 24±2 h. The secondary outcome variables were right ventricular output (RVO), anterior cerebral artery (ACA) blood flow velocity (BFV), superior mesenteric artery (SMA)-BFV and venous hematocrit at 24±2 h, peak total serum bilirubin (TSB), incidences of polycythemia, intraventricular hemorrhage, respiratory distress, feeding intolerance, and necrotizing enterocolitis, outcome, duration of hospital stay, screening audiometry, and serum ferritin levels at the postnatal age of 3 months. Compared to ECC, DCC was associated with significantly higher SVC flow (101.22±21.02 and 81.27±19.12 mL/kg/min, in DCC and ECC groups, respectively; p<0.0001), and significantly increased RVO, SMA-BFV, venous hematocrit, and serum ferritin levels. Though peak TSB was significantly higher with DCC, duration of phototherapy was comparable. ACA-BFV, incidence of polycythemia, and other outcomes were comparable between the groups.Conclusions: DCC was a safe and beneficial intervention in IUGR infants with an improved SBF and SMA-BFV and an increased hematocrit and serum ferritin levels without higher incidences of polycythemia and requirement of phototherapy for significant hyperbilirubinemia.Trial registration: Clinical Trials Registry of India (CTRI/2019/05/018904) What is Known: • Delayed cord clamping (DCC) increases superior vena cava (SVC) blood flow in preterm neonates. • DCC increases hematocrit and serum ferritin in intrauterine growth-restricted (IUGR) neonates, but there may be an associated risk of polycythemia and neonatal hyperbilirubinemia. What is New: • DCC increases SVC blood flow, right ventricular output, superior mesenteric artery blood flow velocity, venous hematocrit, and serum ferritin in IUGR neonates. • Incidences of polycythemia and duration of phototherapy for significant neonatal hyperbilirubinemia do not increase with DCC.

Cytosolic aromatic aldehyde dehydrogenase provides benzoic acid for xanthone biosynthesis in Hypericum.

Benzoic acid is a building block of a multitude of well-known plant natural products, such as paclitaxel and cocaine. Its simple chemical structure contrasts with its complex biosynthesis. Hypericum species are rich in polyprenylated benzoic acid-derived xanthones, which have received attention due to their biological impact on human health. The upstream biosynthetic sequence leading to xanthones is still incomplete. To supply benzoic acid for xanthone biosynthesis, Hypericum calycinum cell cultures use the CoA-dependent non-ß-oxidative pathway, which starts with peroxisomal cinnamate CoA-ligase (HcCNL). Here, we use the xanthone-producing cell cultures to identify the transcript for benzaldehyde dehydrogenase (HcBD), a pivotal player in the non-ß-oxidative pathways. In addition to benzaldehyde, the enzyme efficiently catalyzes the oxidation of trans-cinnamaldehyde in vitro. The enzymatic activity is strictly dependent on the presence of NAD+ as co-factor. HcBD is localized to the cytosol upon ectopic expression of reporter fusion constructs. HcBD oxidizes benzaldehyde, which moves across the peroxisome membrane, to form benzoic acid. Increases in the HcCNL and HcBD transcript levels precede the elicitor-induced xanthone accumulation. The current work addresses a crucial step in the yet incompletely understood CoA-dependent non-ß-oxidative route of benzoic acid biosynthesis. Addressing this step may offer a new biotechnological tool to enhance product formation in biofactories.

A promiscuous coenzyme A ligase provides benzoyl-coenzyme A for xanthone biosynthesis in Hypericum.

Benzoic acid-derived compounds, such as polyprenylated benzophenones and xanthones, attract the interest of scientists due to challenging chemical structures and diverse biological activities. The genus Hypericum is of high medicinal value, as exemplified by H. perforatum. It is rich in benzophenone and xanthone derivatives, the biosynthesis of which requires the catalytic activity of benzoate-coenzyme A (benzoate-CoA) ligase (BZL), which activates benzoic acid to benzoyl-CoA. Despite remarkable research so far done on benzoic acid biosynthesis in planta, all previous structural studies of BZL genes and proteins are exclusively related to benzoate-degrading microorganisms. Here, a transcript for a plant acyl-activating enzyme (AAE) was cloned from xanthone-producing Hypericum calycinum cell cultures using transcriptomic resources. An increase in the HcAAE1 transcript level preceded xanthone accumulation after elicitor treatment, as previously observed with other pathway-related genes. Subcellular localization of reporter fusions revealed the dual localization of HcAAE1 to cytosol and peroxisomes owing to a type 2 peroxisomal targeting signal. This result suggests the generation of benzoyl-CoA in Hypericum by the CoA-dependent non-ß-oxidative route. A luciferase-based substrate specificity assay and the kinetic characterization indicated that HcAAE1 exhibits promiscuous substrate preference, with benzoic acid being the sole aromatic substrate accepted. Unlike 4-coumarate-CoA ligase and cinnamate-CoA ligase enzymes, HcAAE1 did not accept 4-coumaric and cinnamic acids, respectively. The substrate preference was corroborated by in silico modeling, which indicated valid docking of both benzoic acid and its adenosine monophosphate intermediate in the HcAAE1/BZL active site cavity.

Early versus late fortification of breast milk in preterm infants: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the effects of early fortification (EF) versus late fortification (LF) of breast milk (BM) on growth of preterm infants. Randomized and quasi-randomized controlled trials (RCTs) dealing with the effects of EF versus LF on growth parameters, incidence of adverse events, and duration of hospital stay in preterm infants were included. Data were pooled using the RevMan 5.3 software. Quality of evidence for predefined outcomes was analyzed by GRADE. Available evidence (3 RCTs, 309 preterm infants) showed no statistically significant difference between EF and LF of BM for any of the growth parameters-weight (standardized mean difference (SMD) 0.13; 95% confidence interval (CI) - 0.09, 0.36); length (SMD 0.02; 95% CI - 0.20, 0.25); and head circumference (SMD - 0.10; 95% CI - 0.33, 0.12). Total parenteral nutrition days were similar. Duration of hospital stay was significantly higher with EF (MD 4.29; 95% CI 0.84, 7.75) with a trend of non-significant increase in feed intolerance and necrotizing enterocolitis (NEC).Conclusion: Very low quality evidence did not find any significant difference in growth parameters of preterm infants in association with EF or LF of BM. A significant increase in hospital stay and non-significant increase in feed intolerance and NEC were associated with EF.PROSPERO registration number: CRD42019139235What is Known:• Fortification of breast milk with essential macro- and micronutrients is necessary for optimization of nutrition in preterm infants.• There is no consensus regarding the breast milk feeding volume at which fortification should be initiated.What is New:• Very low quality evidence showed no significant difference between early and late fortification of breast milk on growth parameters of preterm infants.• Early fortification was associated with non-significant increase in feed intolerance and necrotizing enterocolitis and a significant increase in hospital stay.

Transcriptome and proteome analyses reveal selenium mediated amelioration of arsenic toxicity in rice (Oryza sativa L.).

Arsenic (As), a chronic poison and non-threshold carcinogen, is a food chain contaminant in rice, posing yield losses as well as serious health risks. Selenium (Se), a trace element, is a known antagonist of As toxicity. In present study, RNA seq. and proteome profiling, along with morphological analyses were performed to explore molecular cross-talk involved in Se mediated As stress amelioration. The repair of As induced structural deformities involving disintegration of cell wall and membranes were observed upon Se supplementation. The expression of As transporter genes viz., NIP1;1, NIP2;1, ABCG5, NRAMP1, NRAMP5, TIP2;2 as well as sulfate transporters, SULTR3;1 and SULTR3;6, were higher in As + Se compared to As alone exposure, which resulted in reduced As accumulation and toxicity. The higher expression of regulatory elements like AUX/IAA, WRKY and MYB TFs during As + Se exposure was also observed. The up-regulation of GST, PRX and GRX during As + Se exposure confirmed the amelioration of As induced oxidative stress. The abundance of proteins involved in photosynthesis, energy metabolism, transport, signaling and ROS homeostasis were found higher in As + Se than in As alone exposure. Overall, present study identified Se responsive pathways, genes and proteins involved to cope-up with As toxicity in rice.

Microsecond MD Simulation and Multiple-Conformation Virtual Screening to Identify Potential Anti-COVID-19 Inhibitors Against SARS-CoV-2 Main Protease.

The recent pandemic outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raised global health and economic concerns. Phylogenetically, SARS-CoV-2 is closely related to SARS-CoV, and both encode the enzyme main protease (Mpro/3CLpro), which can be a potential target inhibiting viral replication. Through this work, we have compiled the structural aspects of Mpro conformational changes, with molecular modeling and 1-µs MD simulations. Long-scale MD simulation resolves the mechanism role of crucial amino acids involved in protein stability, followed by ensemble docking which provides potential compounds from the Traditional Chinese Medicine (TCM) database. These lead compounds directly interact with active site residues (His41, Gly143, and Cys145) of Mpro, which plays a crucial role in the enzymatic activity. Through the binding mode analysis in the S1, S1', S2, and S4 binding subsites, screened compounds may be functional for the distortion of the oxyanion hole in the reaction mechanism, and it may lead to the inhibition of Mpro in SARS-CoV-2. The hit compounds are naturally occurring compounds; they provide a sustainable and readily available option for medical treatment in humans infected by SARS-CoV-2. Henceforth, extensive analysis through molecular modeling approaches explained that the proposed molecules might be promising SARS-CoV-2 inhibitors for the inhibition of COVID-19, subjected to experimental validation.

Malaria risk map for India based on climate, ecology and geographical modelling.

Mapping the malaria risk at various geographical levels is often undertaken considering climate suitability, infection rate and/or malaria vector distribution, while the ecological factors related to topography and vegetation cover are generally neglected. The present study abides a holistic approach to risk mapping by including topographic, climatic and vegetation components into the framework of malaria risk modelling. This work attempts to delineate the areas of Plasmodium falciparum and Plasmodium vivax malaria transmission risk in India using seven geo-ecological indicators: temperature, relative humidity, rainfall, forest cover, soil, slope, altitude and the normalized difference vegetation index using multi-criteria decision analysis based on geographical information system (GIS). The weight of the risk indicators was assigned by an analytical hierarchical process with the climate suitability (temperature and humidity) data generated using fuzzy logic. Model validation was done through both primary and secondary datasets. The spatio-ecological model was based on GIS to classify the country into five zones characterized by various levels of malaria transmission risk (very high; high; moderate; low; and very low. The study found that about 13% of the country is under very high malaria risk, which includes the malaria- endemic districts of the states of Chhattisgarh, Odisha, Jharkhand, Tripura, Assam, Meghalaya and Manipur. The study also showed that the transmission risk suitability for P. vivax is higher than that for P. falciparum in the Himalayan region. The field study corroborates the identified malaria risk zones and highlights that the low to moderate risk zones are outbreak-prone. It is expected that this information will help the National Vector Borne Disease Control Programme in India to undertake improved surveillance and conduct target based interventions.

Infantile tremor syndrome: current perspectives.

Infantile Tremor Syndrome (ITS) is a self-limiting clinical state characterized by tremors, anemia, pigmentary skin disease, regression of mental development, and hypotonia of muscles in a plump looking child. Tremors are coarse in character, decreased or disappeared in sleep and resolves within 4-6 weeks in its natural course. Various etiological factors as infectious, metabolic, nutritional have been hypothesized but none is conclusive. Consensus is developing on the role of Vitamin B12 deficiency in children with ITS but is still debatable. Empirical management of ITS children has been tried in the absence of exact etiology considering child as undernourished. Nutritional management includes supplementation of Iron, Calcium, Magnesium, Vitamin B12 and other multivitamins. Tremors can be managed with administration of propranolol most commonly or phenobarbitone, phenytoin, and carbamazepine.

A multifaceted rhizobacterium Paenibacillus lentimorbus alleviates nutrient deficiency-induced stress in Cicer arietinum L.

Nutrient deficiency in soil is one of the limiting factors responsible for stunted growth and poor flowering/fruiting of crops which result in decline in overall agricultural productivity. However, one important strategy to overcome the problem of nutrient deficiency and to avoid use of chemical fertilizers is the use of plant growth promoting rhizobacteria (PGPR). Paenibacillus lentimorbus NRRL B-30488 (hereafter B-30488), an efficient PGPR has been reported to have various plant growth promoting traits that help crops to mitigate various environmental stresses. Therefore, the present work was designed to examine the application of B-30488 on chickpea growth under nutrient stress condition. Plants inoculated with B-30488 showed positive modulation in physio-biochemical behaviour and mineral nutrient uptake for better growth and development. Alteration in gene expression and metabolic profile under nutrient stress condition in chickpea also supported the stress amelioration capability of B-30488. Principal component analysis statistically proved that improved growth performance of chickpea plants under nutrient stress was mainly due to B-30488 induced modulation of metabolic pathways. To the best of our knowledge, this is the first study for analysis of growth promotion and stress alleviation in chickpea plants subjected to nutrient stress in presence of PGPR B-30488.

Tribulus terrestris improves metronidazole-induced impaired fertility in the male mice.

INTRODUCTION: Fruit extract of Tribulus terrestris (TT) bears aphrodisiac and antioxidative properties. Antimicrobial drug, metronidazole (MTZ) impairs the spermatogenic activity and fertility in males. OBJECTIVE: Validation of the use of fruit extract of TT as a supplement against MTZ-induced fertility impairment in males. METHODS: Adult Swiss strain male mice were administered with 500mg/kgBW/day of MTZ for 28 days. Low (100mg/kgBW/day) and high (200mg/kgBW/day) doses of TT were administered simultaneously with MTZ (500mg/kgBW/day) for same duration. All males were cohabited with virgin proestrus females. Vaginal plug formation was observed to calculate the libido index. Cohabited females were sacrificed on fifteenth day of gestation to dissect out the ovaries and uteri. Fertility index, quantal pregnancy, pre-implantation and post-implantation losses were calculated. RESULTS: MTZ-treated males showed unaltered mating ability, however, the females impregnated by such males exhibited marked alterations in the fertility index, quantal pregnancy and pre- and post-implantation losses. Supplementation with low dose of TT failed to restore such reproductive toxicities exhibited by administration of MTZ. However, the altered reproductive toxicities were reinstated to control values following supplementation with high dose of TT. CONCLUSION: The fruit extract of TT may emerge as an effective herbal remedy, correcting the drug-induced fertility impairments in males.

Fragment-Based De Novo Design of Cyclin-Dependent Kinase 2 Inhibitors.

Cyclin-dependent kinases (CDKs) are core components of the cell cycle machinery that govern the transition between phases during cell cycle progression. Abnormalities in CDKs activity and regulation are common features of cancer, making CDK family members attractive targets for the development of anticancer drugs. One of the main bottlenecks hampering the development of drugs for kinase is the difficulty to attain selectivity. A huge variety of small molecules have been reported as CDK inhibitors, as potential anticancer agents, but none of these has been approved for commercial use. Computer-based molecular design supports drug discovery by suggesting novel new chemotypes and compound modifications for lead candidate optimization. One of the methods known as de novo ligand design technique has emerged as a complementary approach to high-throughput screening. Several automated de novo software programs have been written, which automatically design novel structures to perfectly fit in known binding site. The de novo design supports drug discovery assignments by generating novel pharmaceutically active agents with desired properties in a cost as well as time efficient approach. This chapter describes procedure and an overview of computer-based molecular de novo design methods on a conceptual level with successful examples of CDKs inhibitors.

CDRI-08 Attenuates REST/NRSF-Mediated Expression of NMDAR1 Gene in PBDE-209-Exposed Mice Brain.

CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1) and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg) during PND 3-10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively. The findings showed upregulated expression of NR1 and decreased binding of REST/NRSF to NR1 promoter after postnatal exposure of PBDE-209. Interestingly, supplementation with CDRI-08 significantly restored the expression of NR1 and binding of REST/NRSF to NR1 promoter near to the control value at the dose of 120 mg/kg. In conclusion, the results suggest that CDRI-08 possibly acts on glutamatergic system through expression and regulation of NR1 and may restore memory, impaired by PBDE-209 as reported in our previous study.

Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse.

OBJECTIVE: The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. MATERIALS AND METHODS: Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. RESULTS: Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. CONCLUSION: The fruit extract of TT ameliorates the MTZ-induced alterations in the testis.

Saraca indica bark extract shows in vitro antioxidant, antibreast cancer activity and does not exhibit toxicological effects.

Medicinal plants are used as a complementary and alternative medicine in treatment of various diseases including cancer worldwide, because of their ease of accessibility and cost effectiveness. Multicomposed mixture of compounds present in a plant extract has synergistic activity, increases the therapeutic potential many folds, compensates toxicity, and increases bioavailability. Saraca indica (family Caesalpiniaceae) is one of the most ancient sacred plants with medicinal properties, exhibiting a number of pharmacological effects. Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca indica bark extract (SIE) were carried out in the present study. The results of the study indicated that this herbal preparation has antioxidant and antibreast cancer activity. Toxicological studies suggest that SIE is safer to use and may have a potential to be used as complementary and alternative medicine for breast cancer therapy.

Neuromodulatory role of Bacopa monnieri on oxidative stress induced by postnatal exposure to decabromodiphenyl ether (PBDE -209) in neonate and young female mice.

OBJECTIVES: Bacopa monnieri (BM), a traditional ayurvedic medicine, is a well-known memory enhancer. We have explored the role of BM against decabrominated diphenyl ether (PBDE-209)-induced alterations in neonate and young female mice. MATERIALS AND METHODS: Mice were orally administered with B. monnieri at the doses of 40, 80 or 120 mg/kg body weight along with PBDE-209 (20 mg/kg body weight) from postnatal day (PND) 3-10. Levels of malondialdehyde, protein carbonyl and activities of superoxide dismutase and glutathione peroxidase were measured at both ages. The correct choices and reference/working memory errors of young mice were evaluated by Morris water and radial arm maze. RESULTS: The results showed that BM at the dose of 120 mg/kg significantly (P<0.05) restored the levels of oxidants and the activities of antioxidant enzymes in frontal cortex and hippocampus of neonates against PBDE-209-induced toxicity. CONCLUSION: BM plays a neuroprotective role against PBDE-209-induced alterations in oxidative status.