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1.
J Family Med Prim Care ; 13(5): 2037-2043, 2024 May.
Article in English | MEDLINE | ID: mdl-38948635

ABSTRACT

Background: Hypertension is one of the leading causes of death worldwide, affecting over one billion people. It is responsible for roughly half of all heart disease and stroke-related deaths globally. Because hypertension does not cause any symptoms on its own, it is commonly referred to as "the silent killer." Objective: This study aimed to determine (1) the prevalence of hypertension and its associated risk factors and (2) the level of awareness of hypertension status among study participants. Material and Methods: A facility-based cross-sectional analytical study was conducted for 3 months during January-March 2023 at the teaching institution in Etawah District, Uttar Pradesh. It was conducted among 392 study participants who were ≥18 years old. Data were collected through a predesigned, pretested, semi-structured questionnaire, and anthropometric measurement was determined using standard guidelines. Results: The overall prevalence of hypertension screening was 69.4% (male: 33.8% and female: 66.2%), respectively. The majority of hypertensives were found in female participants. Tobacco and alcohol consumption, obesity, physical inactivity, stress and strain, and an unhealthy diet were also associated with hypertension. Among 392 study participants, only 67 (24.6%) were aware of their hypertension status. Conclusion: We conclude that hypertension has been described as an "Iceberg disease" as those who suffer are usually unaware and hence usually seek healthcare services at a very late stage. Preventive measures should be needed to improve hypertension screening, awareness, treatment, and control.

2.
Plant Physiol Biochem ; 214: 108852, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38943878

ABSTRACT

Abiotic stress such as salt, heavy metals, drought, temperature, and others can affect plants from seed germination to seedling growth to reproductive maturity. Abiotic stress increases reactive oxygen species and lowers antioxidant enzymes in plants resulted the plant tolerance ability against stress conditions decrease. Hydrogen sulfide (H2S) and nitric oxide (NO) are important gasotransmitters involved in seed germination, photosynthesis, growth and development, metabolism, different physiological processes and functions in plants. In plants, various enzymes are responsible for the biosynthesis of both H2S and NO via both enzymatic and non-enzymatic pathways. They also mediate post-translation modification, such as persulfidation, and nitrosylation, which are protective mechanisms against oxidative damage. They also regulate some cellular signalling pathways in response to various abiotic stress. H2S and NO also stimulate biochemical reactions in plants, including cytosolic osmoprotectant accumulation, reactive oxygen species regulation, antioxidant system activation, K+ uptake, and Na+ cell extrusion or vacuolar compartmentation. In this review, we summarize how H2S and NO interact with each other, the function of both H2S and NO, the mechanism of biosynthesis, and post-translational modification under different abiotic stress. Our main emphasis was to find the cross-talk between NO and H2S and how they regulate genes in plants under abiotic stress.

3.
Plant Physiol Biochem ; 208: 108419, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38377888

ABSTRACT

Withania somnifera (Ashwagandha), is one of the most reputed Indian medicinal plants, having immense pharmacological activities due to the occurrence of withanolides. The withanolides are biosynthesized through triterpenoid biosynthetic pathway with the involvement of WsCAS leading to cyclization of 2, 3 oxidosqualene, which is a key metabolite to further diversify to a myriad of phytochemicals. In contrast to the available reports on the studies of WsCAS in withanolide biosynthesis, its involvement in phytosterol biosynthesis needs investigation. Present work deals with the understanding of role of WsCAS triterpenoid synthase gene in the regulation of biosynthesis of phytosterols & withanolides. Docking studies of WsCAS protein revealed Conserved amino acids, DCATE motif, and QW motif which are involved in efficient substrate binding, structure stabilization, and catalytic activity. Overexpression/silencing of WsCAS leading to increment/decline of phytosterols confers its stringent regulation in phytosterols biosynthesis. Differential regulation of WsCAS on the metabolic flux towards phytosterols and withanolide biosynthesis was observed under abiotic stress conditions. The preferential channelization of 2, 3 oxidosqualene towards withanolides and/or phytosterols occurred under heat/salt stress and cold/water stress, respectively. Stigmasterol and ß-sitosterol showed major contribution in high/low temperature and salt stress, and campesterol in water stress management. Overexpression of WsCAS in Arabidopsis thaliana led to the increment in phytosterols in general. Thus, the WsCAS plays important regulatory role in the biosynthetic pathway of phytosterols and withanolides under abiotic stress conditions.


Subject(s)
Phytosterols , Squalene/analogs & derivatives , Triterpenes , Withania , Withanolides , Withanolides/metabolism , Sterols , Withania/genetics , Withania/metabolism , Triterpenes/metabolism , Dehydration , Phytosterols/metabolism , Stress, Physiological/genetics
4.
Phytother Res ; 38(3): 1695-1714, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38318763

ABSTRACT

Withania somnifera, the plant named Indian ginseng, Ashwagandha, or winter cherry, has been used since ancient times to cure various health ailments. Withania somnifera is rich in constituents belonging to chemical classes like alkaloids, saponins, flavonoids, phenolic acids, and withanolides. Several chemotypes were identified based on their phytochemical composition and credited for their multiple bioactivities. Besides, exhibiting neuroprotective, immunomodulatory, adaptogenic, anti-stress, bone health, plant has shown promising anti-cancer properties. Several withanolides have been reported to play a crucial role in cancer; they target cancer cells by different mechanisms such as modulating the expression of tumor suppressor genes, apoptosis, telomerase expression, and regulating cell signaling pathway. Though, many treatments are available for cancer; however, to date, no assured reliable cure for cancer is made available. Additionally, synthetic drugs may lead to development of resistance in time; therefore, focus on new and natural drugs for cancer therapeutics may prove a longtime effective alternative. This current report is a comprehensive combined analysis upto 2023 with articles focused on bio-activities of plant Withania somnifera from various sources, including national and international government sources. This review focuses on understanding of various mechanisms and pathways to inhibit uncontrolled cell growth by W. somnifera bioactives, as reported in literature. This review provides a recent updated status of the W. somnifera on pharmacological properties in general and anti-cancer in particular and may provide a guiding resource for researchers associated with natural product-based cancer research and healthcare management.


Subject(s)
Withania , Withanolides , Withanolides/pharmacology , Withania/chemistry , Plant Extracts/pharmacology , Phytochemicals
5.
J Asian Nat Prod Res ; : 1-15, 2024 Feb 04.
Article in English | MEDLINE | ID: mdl-38311941

ABSTRACT

Based on the major components in the leaves, the ashwagandha has been found to exist in several chemotypic forms in India. From the leaves of various accessions of Withania somnifera, which were maintained in our institute, three new steroids namely, 4-acetoxy-20ß-hydroxy-1-oxo-witha-2,5,24-trienolide (7), 24,25-dihydro-14α-hydroxy withanolide D (9), 5α,6ß,17α,27-tetrahydroxy-1-oxo-witha-2,24-dienolide (12) together with thirteen known withanolides were identified by spectroscopic methods. From the roots and stem of one accession and leaves of another, a new alkyl ester glucoside (4) has also been isolated. The new withanolides 7, 9 and 12 have been tentatively named as withanolide 135 A, withanolide 135B and withanolide 108, respectively.

7.
Access Microbiol ; 4(3): 000327, 2022.
Article in English | MEDLINE | ID: mdl-35693464

ABSTRACT

Zygomycetes have been known to cause life-threatening infections in humans which are often difficult to treat. We present a rare case of cutaneous mucormycosis in a premature neonate admitted with neonatal sepsis and necrotizing fasciitis. He was diagnosed with Lichtheimia ramosa infection and managed surgically along with Amphotericin B. Low birth weight, prematurity, respiratory distress, administration of corticosteroid and broad spectrum antibiotics were identified as the potential risk factors in this case which had led to the fungal infection. Early diagnosis and prompt management is critical in prevention of morbidity and mortality associated with the disease.

8.
Planta ; 256(1): 4, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35648276

ABSTRACT

MAIN CONCLUSION: Overexpression of a novel geranylgeranyl pyrophosphate synthase gene (WsGGPPS) in planta resulted in increased levels of gibberellic acid and decrease in withanolide content. Withania somnifera (L.) Dunal, the herb from family Solanaceae is one of the most treasured medicinal plant used in traditional medicinal systems owing to its unique stockpile of pharmaceutically active secondary metabolites. Phytochemical and pharmacological studies in this plant were well established, but the genes affecting the regulation of biosynthesis of major metabolites were not well elucidated. In this study cloning and functional characterization of a key enzyme in terpenoid biosynthetic pathway viz. geranylgeranyl pyrophosphate synthase (EC 2.5.1.29) gene from Withania somnifera was performed. The full length WsGGPPS gene contained 1,104 base pairs that encode a polypeptide of 365 amino acids. The quantitative expression analysis suggested that WsGGPPS transcripts were expressed maximally in flower tissues followed by berry tissues. The expression levels of WsGGPPS were found to be regulated by methyl jasmonate (MeJA) and salicylic acid (SA). Amino acid sequence alignment and phylogenetic studies suggested that WsGGPPS had close similarities with GGPPS of Solanum tuberosum and Solanum pennellii. The structural analysis provided basic information about three dimensional features and physicochemical parameters of WsGGPPS protein. Overexpression of WsGGPPS in planta for its functional characterization suggested that the WsGGPPS was involved in gibberellic acid biosynthesis.


Subject(s)
Withania , Withanolides , Cloning, Molecular , Gene Expression Regulation, Plant , Geranylgeranyl-Diphosphate Geranylgeranyltransferase/metabolism , Gibberellins , Phylogeny , Withania/genetics , Withanolides/metabolism
9.
Mol Biol Rep ; 49(6): 4555-4563, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35526254

ABSTRACT

BACKGROUND: The flux of isoprenoids and the total accumulation of triterpenoid saponins known as centellosides in C. asiatica are controlled by the key genes of the Mevalonate pathway (MVA). These genes were reported to have positive regulation of the pathway in providing isoprenoid moieties. Though, some information is available on the pathway and secondary metabolites. However, most of the pathway steps are not characterized functionally. METHODOLOGY AND RESULTS: For the study, full-length pathway gene Hydroxymethyl glutaryl-CoA-synthase (CaHMGS; GenBank accession number: MZ997833), was isolated from previously annotated transcriptome data of Centella asiatica leaves. HMGS has been successfully cloned and heterologously expressed in bacteria E. coli strain DH5α. The cloned gene has been sequenced and further characterized through in silico studies by different bioinformatics tools. Also, the gene sequences have been submitted in NCBI. In silico studies of isolated gene sequence revealed the nature, characteristics of genes. The ORF of HMGS is 1449 bp encoding 482 amino acids. Predicted molecular weight (MW) of HMGS was 48.09 kDa and theoretical pI was 5.97. Blast results and Multiple sequence alignments of the gene showing the similarity with HMGS of other plants of their respective families. The Molecular Evolutionary Genetic Analysis (MEGA) version 10.1.6 was used to construct a phylogenetic tree. Differential tissue-specific expression of different plant parts was also checked. Tissue expression patterns unveiled that the highest expression level of the CaHMGS had been seen in the roots and lowest in the node of the plant. Functional complementation experiment of the CaHMGS in Saccharomyces cerevisiae wild strain YSC1021 and haploid strain YSC1021 which lack HMGS protein confirmed that the CaHMGS gene encodes functional CaHMGS that catalyzed the biosynthesis of mevalonate in yeast. CONCLUSIONS: The gene was reported, cloned and characterized first time in Centella asiatica. Understanding this biosynthetic pathway gene will further help in the improvement of plants for enhanced secondary metabolites production.


Subject(s)
Centella , Triterpenes , Biosynthetic Pathways/genetics , Centella/genetics , Centella/metabolism , Cloning, Molecular , Escherichia coli/genetics , Escherichia coli/metabolism , Humans , Mevalonic Acid/metabolism , Phylogeny , Terpenes
11.
J Ethnopharmacol ; 278: 114296, 2021 Oct 05.
Article in English | MEDLINE | ID: mdl-34090907

ABSTRACT

ETHNO-PHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal, commonly known as Ashwagandha, belongs to the family Solanaceae. In Ayurveda, Ashwagandha has been defined as one of the most important herb and is considered to be the best adaptogen. It is also an excellent rejuvenator, a general health tonic and cure for various disorders such as cerebrovascular, insomnia, asthma, ulcers, etc. Steroidal lactones (Withanolides: Withanolide A, Withaferin A, Withanolide D, Withanone, etc) isolated from this plant, possess promising medicinal properties such as anti-inflammatory, immune-stimulatory etc. Standardized root extract of the plant NMITLI-118R (NM) was prepared at CSIR-CIMAP, and was investigated for various biological activities at CSIR-CDRI. Among the notable medicinal properties, NM exhibited excellent neuroprotective activity in the middle cerebral artery occlusion (MCAO) rat model. AIM OF THE STUDY: Endothelial dysfunction is the primary event in the cerebrovascular or cardiovascular disorders, present study was thus undertaken to evaluate vasoprotective potential of NM and its biomarker compound Withanolide A (WA) using rat aortic rings and EA.hy926 endothelial cells. MATERIAL AND METHODS: Transverse aortic rings of 10 weeks old Wistar rats were used to evaluate effect of NM and WA on the vasoreactivity. While, mechanism of NM and WA mediated vasorelaxant was investigated in Ea.hy926 cell line by measuring NO generation, nitrite content, Serine 1177 phosphorylation of eNOS, reduced/oxidized biopterin levels and expression of endothelial nitric oxide synthase (eNOS) mRNA and protein. RESULTS: Fingerprinting of NM using HPLC identified presence of WA in the extract. NM as well as WA exerted moderate vasorelaxant effect in the endothelium intact rat aortic rings which was lesser than acetylcholine (ACh). NM and WA augmented ACh induced relaxation in the rat aortic rings. NM and WA dependent vasorelaxation was blocked by N-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4] oxadiazolo [4,3,-a]quinoxalin-1-one (ODQ), indicating role of NO/cGMP. Further Ea.hy926 cells treated with NM and WA showed accumulation of nitrite content, enhanced NO levels, eNOS expression and eNOS phosphorylation (Serine 1177). CONCLUSION: Altogether NM and WA dependent improvement in the NO availability seems to be mediated by the enhanced eNOS phosphorylation. WA, seems to be one of the active constituent of NM, and presence of other vasoactive substances cannot be ruled out. The data obtained imply that the vasorelaxant property of NM is beneficial for its neuroprotective potential.


Subject(s)
Aorta/drug effects , Nitric Oxide/metabolism , Plant Extracts/pharmacology , Vasodilator Agents/pharmacology , Withania/chemistry , Withanolides/pharmacology , Animals , Biomarkers , Cell Line , Cell Proliferation , Endothelial Cells/drug effects , Male , Plant Extracts/chemistry , Plant Roots/chemistry , Rats , Rats, Wistar , Vasoconstriction/drug effects , Vasodilator Agents/chemistry , Withanolides/chemistry
12.
J Ethnopharmacol ; 270: 113819, 2021 Apr 24.
Article in English | MEDLINE | ID: mdl-33460762

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Withanone (WN), an active constituent of Withania somnifera commonly called Ashwagandha has remarkable pharmacological responses along with neurological activities. However, for a better understanding of the pharmacokinetic and pharmacodynamic behavior of WN, a comprehensive in-vitro ADME (absorption, distribution, metabolism, and excretion) studies are necessary. AIM OF THE STUDY: A precise, accurate, and sensitive reverse-phase ultra-performance liquid chromatographic method of WN was developed and validated in rat plasma for the first time. The developed method was successfully applied to the in-vitro ADME investigation of WN. MATERIAL AND METHODS: The passive permeability of WN was assayed using PAMPA plates and the plasma protein binding (PPB) was performed using the equilibrium dialysis method. Pooled liver microsomes of rat (RLM) and human (HLM) were used for the microsomal stability, CYP phenotyping, and inhibition studies. CYP phenotyping was evaluated using the specific inhibitors. CYP inhibition study was performed using specific probe substrates along with WN or specific inhibitors. RESULTS: WN was found to be stable in the simulated gastric and intestinal environment and has a high passive permeability at pH 4.0 and 7.0 in PAMPA assay. The PPB of WN at 5 and 20 µg/mL concentrations were found to be high i.e. 82.01 ± 1.44 and 88.02 ± 1.15%, respectively. The in vitro half-life of WN in RLM and HLM was found to be 59.63 ± 2.50 and 68.42 ± 2.19 min, respectively. CYP phenotyping results showed that WN was extensively metabolized by CYP 3A4 and1A2 enzymes in RLM and HLM. However, the results of CYP Inhibition studies showed that none of the CYP isoenzymes were potentially inhibited by WN in RLM and HLM. CONCLUSION: The in vitro results of pH-dependent stability, plasma stability, permeability, PPB, blood partitioning, microsomal stability, CYP phenotyping, and CYP inhibition studies demonstrated that WN could be a better phytochemical for neurological disorders.


Subject(s)
Blood Proteins/metabolism , Chromatography, High Pressure Liquid/methods , Cytochrome P-450 Enzyme Inhibitors/pharmacology , Cytochrome P-450 Enzyme System/metabolism , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Withanolides/pharmacology , Animals , Humans , Isoenzymes/drug effects , Isoenzymes/metabolism , Male , Microsomes, Liver/metabolism , Neuroprotective Agents/isolation & purification , Neuroprotective Agents/metabolism , Permeability/drug effects , Plant Extracts/isolation & purification , Plant Extracts/metabolism , Protein Binding/drug effects , Rats , Rats, Sprague-Dawley , Withania/chemistry , Withanolides/isolation & purification , Withanolides/metabolism
13.
Ann Indian Acad Neurol ; 24(5): 771-773, 2021.
Article in English | MEDLINE | ID: mdl-35002143
14.
Mol Biol Rep ; 47(9): 6587-6598, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32860161

ABSTRACT

Genus Ocimum is known to have species possessing important therapeutic essential oil. The major phytoconstituents of essential oil in Ocimum species are phenylpropanoids and terpenoids. The essential oil is accumulated in the trichomes; the specialized structures predominantly found on leaves and other tissues. The development of trichome is integrated with development of plant and leaf and also tightly coordinated with the primary and secondary metabolic pathways producing essential oil constituents. In continuation to our studies on elucidating/understanding the mechanism of biosynthesis of  essential oil pathways in Ocimum species, we have performed comparative transcriptome analysis to investigate the role of trichome-related gene expression in the regulation of biosynthetic pathways of essential oil. The essential oil biogenesis is tightly integrated with primary metabolic activities, the analysis for the expression pattern of genes related to primary metabolism and its relationship with secondary metabolism was evaluated in comparative manner. Physiological parameters in relation to primary metabolism such as photosynthetic pigment content, soluble sugar content, and invertase enzymes along with morphological parameters were analysed in O. basilicum and O. sanctum. Differential expression profiling uncovered about 8116 and 2810 differentially expressed transcripts in O. basilicum and O. sanctum, respectively. Enrichment of differentially expressed genes were analysed in relation to metabolic pathways, primary metabolism and secondary metabolism. Trichome related genes identified from the Ocimum species vis-à-vis their expression profiles suggested higher expression in O. basilicum. The findings in this study provide interesting insights into the role of trichome-related transcripts in relation to essential oil content in Ocimum species. The study is valuable as this is the first study on revealing the transcripts and their role in trichome development and essential oil biogenesis in two major species of Ocimum.


Subject(s)
Ocimum/chemistry , Ocimum/metabolism , Oils, Volatile/metabolism , Transcriptome/genetics , Trichomes/growth & development , Trichomes/metabolism , Gene Expression Profiling , Gene Expression Regulation, Plant/genetics , Gene Ontology , Metabolic Networks and Pathways/genetics , Metabolic Networks and Pathways/physiology , Ocimum/enzymology , Ocimum/genetics , Phylogeny , Plant Leaves/genetics , Plant Leaves/growth & development , Plant Leaves/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Secondary Metabolism/genetics , Secondary Metabolism/physiology , Terpenes/metabolism , Trichomes/chemistry , Trichomes/genetics
15.
Plant Cell Rep ; 39(11): 1443-1465, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32789542

ABSTRACT

KEY MESSAGE: WsWRKY1-mediated transcriptional modulation of Withania somnifera tryptophan decarboxylase gene (WsTDC) helps to regulate fruit-specific tryptamine generation for production of withanamides. Withania somnifera is a highly valued medicinal plant. Recent demonstration of novel indolyl metabolites called withanamides in its fruits (berries) prompted us to investigate its tryptophan decarboxylase (TDC), as tryptophan is invariably a precursor for indole moiety. TDC catalyzes conversion of tryptophan into tryptamine, and the catalytic reaction constitutes a committed metabolic step for synthesis of an array of indolyl metabolites. The TDC gene (WsTDC) was cloned from berries of the plant and expressed in E. coli. The recombinant enzyme was purified and characterized for its catalytic attributes. Catalytic and structural aspects of the enzyme indicated its regulatory/rate-limiting significance in generation of the indolyl metabolites. Novel tissue-wise and developmentally differential abundance of WsTDC transcripts reflected its preeminent role in withanamide biogenesis in the fruits. Transgenic lines overexpressing WsTDC gene showed accumulation of tryptamine at significantly higher levels, while lines silenced for WsTDC exhibited considerably depleted levels of tryptamine. Cloning and sequence analysis of promoter of WsTDC revealed the presence of W-box in it. Follow-up studies on isolation of WsWRKY1 transcription factor and its overexpression in W. somnifera revealed that WsTDC expression was substantially induced by WsWRKY1 resulting in overproduction of tryptamine. The study invokes a key role of TDC in regulating the indolyl secondary metabolites through enabling elevated flux/supply of tryptamine at multiple levels from gene expression to catalytic attributes overall coordinated by WsWRKY1. This is the first biochemical, molecular, structural, physiological and regulatory description of a fruit-functional TDC.


Subject(s)
Aromatic-L-Amino-Acid Decarboxylases/genetics , Plant Proteins/genetics , Tryptamines/biosynthesis , Withania/genetics , Withania/metabolism , Aromatic-L-Amino-Acid Decarboxylases/chemistry , Aromatic-L-Amino-Acid Decarboxylases/metabolism , Cloning, Molecular , Disaccharides/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Gene Expression Regulation, Plant , Indoles/metabolism , Models, Molecular , Phylogeny , Plant Proteins/chemistry , Plant Proteins/metabolism , Plants, Genetically Modified , Plants, Medicinal/genetics , Plants, Medicinal/metabolism , Promoter Regions, Genetic , Transcription Factors/genetics , Transcription Factors/metabolism , Tryptamines/metabolism
16.
Eur J Clin Nutr ; 72(4): 564-571, 2018 04.
Article in English | MEDLINE | ID: mdl-29453428

ABSTRACT

BACKGROUND/OBJECTIVES: To ascertain associations between plasma insulin-like growth factor I (IGF-I), insulin-like growth factor-binding protein 3 (IGFBP-3) and their molar ratio at 2 y with neonatal size, infant growth, body composition at 2 y, and feeding practices in an Indian cohort. SUBJECTS/METHODS: A cohort of 209 newborns, with 122 followed at 2 y. Anthropometry was conducted at birth and 2 y. IGF-I and IGFBP-3 concentrations were measured in cord blood and at 2 y. Maternal and child diet was assessed by food frequency questionnaires and maternal interviews. Multivariate regression was used to test for associations adjusting for confounding factors. RESULTS: Mean 2 y plasma IGF-I and IGFBP-3 concentrations and IGF-I/IGFBP-3 were 49.4 ng/ml (95% CI: 44.1, 54.8), 1953.8 ng/ml (CI: 1870.6, 2036.9) ng/ml, and 0.088 (CI: 0.081, 0.095), respectively. IGF-I and IGF-I/IGFBP-3 were positively associated with current length, but not body mass index or adiposity. IGF-I was higher among those with greater change in length since birth. IGF-I concentrations were higher in children who drank the most milk (>500 vs. <250 ml per day: 65.6 vs. 42.8 ng/ml, p < 0.04), received other milk <6 months compared to ≥6 months (56.3 vs. 44.8 ng/ml, p < 0.05), and in those whose mothers consumed milk daily vs. less frequently in late pregnancy (56.4 vs. 42.7 ng/ml, p < 0.01). In multivariate regression, 2 y IGF-I concentration and IGF-I/IGFBP-3 were each positively associated with current length and milk intake. IGFBP-3 was not related to anthropometry or milk intake. CONCLUSIONS: Plasma IGF-I concentrations and IGF-I/IGFBP-3 at 2 y are positively associated with length at 2 y and current milk intake.


Subject(s)
Diet/statistics & numerical data , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/analysis , Milk , Animals , Anthropometry , Body Height/physiology , Body Mass Index , Breast Feeding/statistics & numerical data , Child, Preschool , Female , Fetal Blood/chemistry , Humans , Infant , Infant, Newborn , Longitudinal Studies , Male , Pregnancy
17.
J Chromatogr Sci ; 55(7): 729-735, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28407087

ABSTRACT

Withanolides are the group of active chemical constituents of Withania somnifera (L.) Dunal. Withaferin A, withanolide A and withanone presents three of the biologically most active constituents of this herb. These steroidal lactones are isomers of each other and thus, pose significant difficulty in their separation. In present study, a simple, specific and reliable RP-HPLC method has been developed and validated for their separation and simultaneous quantification. Separation was carried out on Lichrocart Purospher STAR RP-18e column (250 × 4.5 mm, 5 µm) using mobile phase, methanol and 0.01 M ammonium acetate buffer (pH 5) in the ratio 60:40, v/v. The calibration curves were linear (r2 > 0.99) for all the three compounds across concentration range of 1.56-50 µg/mL. The lower limit of quantification for all the analytes was 1.56 µg/mL. The intra-day and inter-day accuracy was between 88.65% and 110.66% and coefficient of variation was between 0.55 and 10.12. The analytes were stable under different storage conditions. The developed method was successfully applied to analyze the samples for simultaneous determination of permeability of the three withanolides in rats using in situ single-pass intestinal perfusion model. Withanolide A and withanone were found to be high permeability compounds while withaferin A could not be detected.


Subject(s)
Chromatography, High Pressure Liquid/methods , Intestine, Small/metabolism , Withanolides/analysis , Withanolides/isolation & purification , Animals , Intestinal Absorption , Isomerism , Linear Models , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Withanolides/pharmacokinetics
18.
Physiol Plant ; 159(4): 381-400, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27580641

ABSTRACT

Rose-scented geranium (Pelargonium spp.) is one of the most important aromatic plants and is well known for its diverse perfumery uses. Its economic importance is due to presence of fragrance rich essential oil in its foliage. The essential oil is a mixture of various volatile phytochemicals which are mainly terpenes (isoprenoids) in nature. In this study, on the geranium foliage genes related to isoprenoid biosynthesis (DXS, DXR and HMGR) were isolated, cloned and confirmed by sequencing. Further, the first gene of 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, 1-deoxy-d-xylulose-5-phosphate synthase (GrDXS), was made full length by using rapid amplification of cDNA ends strategy. GrDXS contained a 2157 bp open reading frame that encoded a polypeptide of 792 amino acids having calculated molecular weight 77.5 kDa. This study is first report on heterologous expression and kinetic characterization of any gene from this economically important plant. Expression analysis of these genes was performed in different tissues as well as at different developmental stages of leaves. In response to external elicitors, such as methyl jasmonate, salicylic acid, light and wounding, all the three genes showed differential expression profiles. Further GrDXS was over expressed in the homologous (rose-scented geranium) as well as in heterologous (Withania somnifera) plant systems through genetic transformation approach. The over-expression of GrDXS led to enhanced secondary metabolites production (i.e. essential oil in rose-scented geranium and withanolides in W. somnifera). To the best of our knowledge, this is the first report showing the expression profile of the three genes related to isoprenoid biosynthesis pathways operated in rose-scented geranium as well as functional characterization study of any gene from rose-scented geranium through a genetic transformation system.


Subject(s)
Biosynthetic Pathways/genetics , Butadienes/metabolism , Genes, Plant , Geranium/genetics , Hemiterpenes/metabolism , Pentanes/metabolism , Plastids/metabolism , Secondary Metabolism/genetics , Terpenes/metabolism , Withania/genetics , Acetates/pharmacology , Base Sequence , Biocatalysis/drug effects , Biosynthetic Pathways/drug effects , Biosynthetic Pathways/radiation effects , Cloning, Molecular , Computational Biology , Cyclopentanes/pharmacology , Evolution, Molecular , Gene Expression Profiling , Gene Expression Regulation, Plant/drug effects , Gene Expression Regulation, Plant/radiation effects , Geranium/drug effects , Geranium/radiation effects , Light , Oxylipins/pharmacology , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Plastids/drug effects , Plastids/radiation effects , Recombinant Proteins/metabolism , Secondary Metabolism/drug effects , Secondary Metabolism/radiation effects , Sequence Alignment , Sequence Analysis, DNA , Structural Homology, Protein , Withania/drug effects , Withania/radiation effects
19.
Protoplasma ; 254(1): 505-522, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27263081

ABSTRACT

Artemisia annua accumulates substantial quantities of unique and highly useful antimalarial sesquiternoid artemisinin and related phytomolecules as well as its characteristic essential oil in its glandular trichomes. The phytomolecules are mainly produced in its leaves and inflorescences. Artemisia annua plants were grown under NaCl salinity (50, 100 and 200 mM) stress conditions imposed throughout the entire life cycle of the plant. Results revealed that specialized metabolites like artemisinin, arteannuin-B, artemisinic acid + dihydroartemisinic acid and essential oil accumulation were positively modulated by NaCl salinity stress. Interestingly, total content of monoterpenoids and sesquiterpenoids of essential oil was induced by NaCl salinity treatment, contrary to previous observations. Production of camphor, the major essential oil constituent was induced under the influence of treatment. The metabolic acclimation and manifestations specific to terpenoid pathway are analysed vis-a-vis vegetative to reproductive periods and control of the modulation. WRKY and CYP71AV1 play a key role in mediating the responses through metabolism in glandular trichomes. The distinctness of the salinity induced responses is discussed in light of differential mechanism of adaptation to abiotic stresses and their impact on terpenoid-specific metabolic adjustments in A. annua. Results provide potential indications of possible adaptation of A. annua under saline conditions for agrarian techno-economic benefaction.


Subject(s)
Acclimatization/drug effects , Artemisia annua/growth & development , Artemisia annua/metabolism , Metabolome/drug effects , Oils, Volatile/metabolism , Sodium Chloride/pharmacology , Stress, Physiological/drug effects , Terpenes/metabolism , Analysis of Variance , Artemisia annua/drug effects , Artemisia annua/genetics , Artemisinins , Biosynthetic Pathways/drug effects , Biosynthetic Pathways/genetics , Gene Expression Regulation, Plant/drug effects , Proline/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Thiobarbituric Acid Reactive Substances/metabolism , Trichomes/drug effects , Trichomes/metabolism
20.
J Assoc Physicians India ; 64(5): 75-76, 2016 05.
Article in English | MEDLINE | ID: mdl-27735158

ABSTRACT

Esophageal melanocytosis is a rare benign condition characterized by melanocytic proliferation in esophageal squamous epithelium and melanin deposition in the mucosa. Because of its uncommon nature, pathologists and gastroenterologists lack experience with this entity. We present a case of esophageal melanocytosis in a 66 years old male patient who presented with atypical chest pain and dysphagia. Endoscopic guided biopsy was done, provisional diagnosis of esophageal melanocytosis was made. Bleaching and immunohistochemistry confirmed the diagnosis.


Subject(s)
Endoscopy, Digestive System/methods , Esophageal Diseases/pathology , Melanocytes/pathology , Melanosis/pathology , Aged , Biopsy , Deglutition Disorders , Esophagus , Humans , Male , Melanins/metabolism , Melanocytes/metabolism , Melanosis/metabolism
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