Phytochemicals from the stem wood of Sorbus lanata (D. Don.) Schauer

Three new phenolic compounds, sorlanin (4-(3-(hydroxymethyl)-5-methoxy-7-phenyl-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)-2-methoxyphenol, 1), sorbanin (2-((3,5-dimethoxy-[1,1′-biphenyl]-4-yl)oxy)-1-(4-hydroxy-3-methoxyphenyl)propane-1,3-diol, 2) and sorbalanin (4-(3-(hydroxymethyl)-5,6-dimethoxy-2,3-dihydrobenzo[b][1,4]dioxino[2,3-g]benzofuran-2-yl)-2-methoxyphenol, 3), together with eight known compounds, polystachyol (4), isolariciresinol (5), dihydrodehydrodiconiferyl alcohol (6), tuberculatin (7), ovafolinin E (8), aucuparin (9), 2′-methoxyaucuparin (10), and tetracosyl-3-(3,4-dihydroxyphenyl)acrylate (11), were isolated from Sorbus lanata. The structures of these phytoconstituents were elucidated through extensive spectroscopic techniques, including UV, IR, 1D and 2D NMR, ESI-MS and HRESI-MS experiments. All the compounds except 9 and 10 were isolated for the first time from the genus Sorbus. The isolated compounds were also tested in DPPH radical scavenging reaction where compounds 6, 7, 10 and 11 showed significant activities with IC₅₀ values of 9.2, 11.7, 23.0 and 33.7 μM, respectively.     

Exome sequencing discloses <Emphasis Type="Italic">KALRN</Emphasis> homozygous variant as likely cause of intellectual disability and short stature in a consanguineous pedigree

Background

The recent availability of whole-exome sequencing has opened new possibilities for the evaluation of individuals with genetically undiagnosed intellectual disability.

Results

We report two affected siblings, offspring of first-cousin parents, with intellectual disability, hypotonia, short stature, growth hormone deficiency, and delayed bone age. All members of the nuclear family were genotyped, and exome sequencing was performed in one of the affected individuals. We used an in-house algorithm (CATCH v1.1) that combines homozygosity mapping with exome sequencing results and provides a list of candidate variants. One identified novel homozygous missense variant in KALRN (NM_003947.4:c.3644C>A: p.(Thr1215Lys)) was predicted to be pathogenic by all pathogenicity prediction software used (SIFT, PolyPhen, Mutation Taster). KALRN encodes the protein kalirin, which is a GTP-exchange factor protein with a reported role in cytoskeletal remodeling and dendritic spine formation in neurons. It is known that mice with ablation of Kalrn exhibit age-dependent functional deficits and behavioral phenotypes.

Conclusion

Exome sequencing provided initial evidence linking KALRN to monogenic intellectual disability in man, and we propose that KALRN is the causative gene for the autosomal recessive phenotype in this family.

     

Ethnomedicines and anti-parasitic activities of Pakistani medicinal plants against <Emphasis Type="Italic">Plasmodia</Emphasis> and <Emphasis Type="Italic">Leishmania</Emphasis> parasites

Background

Leishmaniasis and malaria are the two most common parasitic diseases and responsible for large number of deaths per year particularly in developing countries like Pakistan. Majority of Pakistan population rely on medicinal plants due to their low socio-economic status. The present review was designed to gather utmost fragmented published data on traditionally used medicinal plants against leishmaniasis and malaria in Pakistan and their scientific validation.

Methods

Pub Med, Google Scholar, Web of Science, ISI Web of knowledge and Flora of Pakistan were searched for the collection of data on ethnomedicinal plants. Total 89 articles were reviewed for present study which was mostly published in English. We selected only those articles in which complete information was given regarding traditional uses of medicinal plants in Pakistan.

Results

Total of 56 plants (malaria 33, leishmaniasis 23) was found to be used traditionally against reported parasites. Leaves were the most focused plant part both in traditional use and in in vitro screening against both parasites. Most extensively used plant families against Leishmaniasis and Malaria were Lamiaceae and Asteraceae respectively. Out of 56 documented plants only 15 plants (Plasmodia 4, Leishmania 11) were assessed in vitro against these parasites. Mostly crude and ethanolic plant extracts were checked against Leishmania and Plasmodia respectively and showed good inhibition zone. Four pure compounds like artemisinin, physalins and sitosterol extracted from different plants proved their efficacy against these parasites.

Conclusions

Present review provides the efficacy and reliability of ethnomedicinal practices and also invites the attention of chemists, pharmacologist and pharmacist to scientifically validate unexplored plants that could lead toward the development of novel anti-malarial and anti-leishmanial drugs.

     

Quantification of biochemical compounds in Bauhinia Variegata Linn flower extract and its hepatoprotective effect

Liver disorders may occur as a result of exposure to chemical compounds capable of inducing the oxidative stress and hepatic injuries. The aim of present study was to investigate the effects of flower extracts of B. Variegata for the treatment of liver injury induced by the CCl₄. About 1 ml/kg body weight (b.w) of CCl4 was induced to experimental mice by intraperitoneal way for 14 days. The methanol and chloroform extracts (100, 200 and 300 mg/kg b.w) were administered to experimental animals for 14 days along with standard drug Silymarine (100 mg/kg b.w). The extracts alone showed no evidence of hepatic toxicity but animals exposed to CCl₄ without the treatment with B. Variegata presented variations in levels of liver enzymes, antioxidant enzymes, proteins and blood cells as well as injuries in liver cells were also observed during histopathological study. However, after the treatments especially with 300 mg/kg b.w of methanol flower extracts levels of liver markers (ALT, AST and ALP), antioxidant enzymes and blood cells decreases and turned towards normal levels. Whereas level of total proteins and bilirubin was improved and damaged liver cells were repaired. The curative activity of flower extracts can be correlated to the higher potential of antioxidants and occurrence of Quercetin and some other organic compounds those were investigated from flower extracts of B. Variegata during HPLC and GC-MS analysis. The finding of this study supports the use of B. Variegata flower formulation in folk medicines.     

Comprehensive report on the prevalence of root-knot nematodes in the Poonch division of Azad Jammu and Kashmir,Pakistan

The present study documents the root-knot nematodes (RKN) fauna of the Poonch division in Azad Jammu and Kashmir infecting vegetables. An overall prevalence of 40% of RKN was recorded. Of the four districts investigated, maximum prevalence was recorded in district Poonch with 59%, followed by Sudhnuti with 58%. The lowest prevalence of RKN was found in districts Bagh (29%) and Haveli (33%). Out of 15 vegetables investigated, RKN was found on five crops. The highest prevalence of 37.8% was recorded on okra, followed by 31.3% on cucumber and 17.5% on tomato. RKN was less prevalent on eggplant (8.3%) and beans (7.7%). Three RKN species, that is Meloidogyne incognita, Meloidogyne javanica and Meloidogyne arenaria, were found infecting the hosts. M. javanica was found to be the most prevalent followed by M. incognita and M. arenaria. This trend was found in all the districts. Overall prevalence of M. javanica as sole population was 9% and that of M. incognita was 2%. Meloidogyne arenaria was not found in any of the fields as sole population. The prevalence of M. incognita with M. javanica or M. arenaria as mixed populations was 8% and 5%, respectively, and that of M. javanica with M. arenaria was 4%. Similarly, all the three species prevailed as mixed populations in 12% of the fields in the division. The severity of RKN infections, measured as galling index, was found to be variable within each infected field (GI 2–9). Identification of RKN species was based on the morphology of perineal patterns and confirmed by molecular SCAR and CO1 makers based identification. In conclusion, RKN were distributed in the Poonch division and M. javanica was predominant. Cucumber, okra, tomato and eggplant were severely attacked by these nematodes warranting the adoption of stringent control strategies for their management.     

Pollen morphology of the genus Euphrasia L. (Orobanchaceae) from Pakistan and Kashmir and its taxonomic significance

Pollen morphology of 25 species of the genus Euphrasia L., belonging to the family Orobanchaceae from Pakistan has been examined by light and scanning electron microscope. It is a stenopalynous genus. Pollen grains are usually radially symmetrical, isopolar, tricolpate, sub-prolate to prolate-spheroidal rarely oblate-spheroidal. Sexine slightly thinner than nexine or as thick as nexine. Tectum coarse to fine retipilate or rugulate–retipilate. On the basis of exine ornamentation three distinct pollen types viz., Euphrasia foliosa, Euphrasia multiflora, and Euphrasia incisa are recognized. Pollen morphology is significantly helpful at specific level within the pollen type.     

Absolute Configuration of Oplopanone Derivatives From Serphidium stenocephalum: ECD Spectra of Acyclic Ketones With Front‐Octant Contributions

The electronic circular dichroism (ECD) spectra of two sesquiterpenoids ( 1 and 2 ) related to oplopanone, obtained from a methanolic extract of the plant Serphidium stenocephalum (Artemisia stenocephala), were measured and reproduced by means of time‐dependent density functional theory (TDDFT) calculations, establishing their absolute configuration. The application of ketone octant rule for carbonyl n‐π* ECD band to compounds 1 and 2 , which include an acyclic carbonyl group, was critically assessed. The peculiar oplopanone skeleton makes a straightforward application of the octant rule impossible, because of the uncertainty related to the shape of the so‐called third nodal surface separating front and back octants. The various group contributions to the carbonyl n‐π* ECD band were estimated with TDDFT calculations on selected molecular models obtained by consecutive dissections from 1 . Chirality 26:39–43, 2013. © 2013 Wiley Periodicals, Inc.     

Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity resulting in significant morbidity and mortality. The pathology of BPD is multifactorial and leads to alveolar simplification and distal lung injury. Previous studies have shown a beneficial effect of systemic treatment with bone marrow-derived mesenchymal stromal cells (MSCs) and MSC-conditioned media (MSC-CM) leading to amelioration of the lung parenchymal and vascular injury in vivo in the hyperoxia murine model of BPD. It is possible that the beneficial response from the MSCs is at least in part due to activation of endogenous lung epithelial stem cells. Bronchioalveolar stem cells (BASCs) are an adult lung stem cell population capable of self-renewal and differentiation in culture, and BASCs proliferate in response to bronchiolar and alveolar lung injury in vivo. Systemic treatment of neonatal hyperoxia-exposed mice with MSCs or MSC-CM led to a significant increase in BASCs compared with untreated controls. Treatment of BASCs with MSC-CM in culture showed an increase in growth efficiency, indicating a direct effect of MSCs on BASCs. Lineage tracing data in bleomycin-treated adult mice showed that Clara cell secretory protein-expressing cells including BASCs are capable of contributing to alveolar repair after lung injury. MSCs and MSC-derived factors may stimulate BASCs to play a role in the repair of alveolar lung injury found in BPD and in the restoration of distal lung cell epithelia. This work highlights the potential important role of endogenous lung stem cells in the repair of chronic lung diseases.     

Detection of common mutations in the GALT gene through ARMS

Type I galactosemia is an inborn error resulting from mutations on both alleles of the GALT gene, which leads to the absence or deficiency of galactose-1-phosphate uridyltranseferase (GALT), the second of three enzymes catalyzing the conversion of galactose into glucose. On the basis of residual GALT activity, Type I galactosemia is classified into severe “Classical” and mild “Duarte” phenotypes. Classical galactosemia is frequently associated with S135L, Q188R and K285N mutations in the GALT gene. The functionally neutral N314D variation in the GALT gene is associated with Duarte galactosemia and is widespread among various worldwide populations. The present study aimed at detecting S135L, Q188R and K285N mutations and the N314D variant in the GALT gene by PCR using amplification refractory mutation system (ARMS). ARMS assays were established using standard DNA samples and were used for 8 galactosemia patients and 190 unrelated normal subjects all of Pakistani origin. S135L and K285N mutations were present neither in galactosemia patients nor in normal subjects. Only one galactosemia patient carried Q188R mutation that was in homozygous state. However, the N314D variant was frequently found both in affected (7 out of 16 alleles) and normal subjects (55 out of 380 alleles). This finding indicates that Duarte allele D314 might be far more common in Pakistani population than in European and North American ones.