scholarly journals Antiarthritic Effects of a Root Extract from Harpagophytum procumbens DC: Novel Insights into the Molecular Mechanisms and Possible Bioactive Phytochemicals

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2545 ◽  
Author(s):  
Alessia Mariano ◽  
Antonella Di Sotto ◽  
Martina Leopizzi ◽  
Stefania Garzoli ◽  
Valeria Di Maio ◽  
...  
Keyword(s):  
Volatile Compounds ◽  
Molecular Mechanisms ◽  
Endocannabinoid System ◽  
Receptor Expression ◽  
Root Extract ◽  
Bioactive Constituents ◽  
Traditional Remedy ◽  
Harpagophytum Procumbens ◽  
First Time ◽  
Synovial Membranes

Harpagophytum procumbens (Burch.) DC. ex Meisn. is a traditional remedy for osteoarticular diseases, including osteoarthritis (OA), although the bioactive constituents and mechanisms involved are yet to be clarified. In the present study, an aqueous H. procumbens root extract (HPE; containing 1.2% harpagoside) was characterized for its effects on synoviocytes from OA patients and phytochemical composition in polyphenols, and volatile compounds were detected. HPE powder was dissolved in different solvents, including deionized water (HPEH2O), DMSO (HPEDMSO), 100% v/v ethanol (HPEEtOH100), and 50% v/v ethanol (HPEEtOH50). The highest polyphenol levels were found in HPEDMSO and HPEEtOH50, whereas different volatile compounds, mainly β-caryophyllene and eugenol, were detected in all the extracts except for HPEH2O. HPEH2O and HPEDMSO were able to enhance CB2 receptor expression and to downregulate PI-PLC β2 in synovial membranes; moreover, all the extracts inhibited FAAH activity. The present results highlight for the first time a multitarget modulation of the endocannabinoid system by HPE, likely ascribable to its hydrosoluble compounds, along with the presence of volatile compounds in H. procumbens root. Although hydrosoluble compounds seem to be mainly responsible for endocannabinoid modulation by HPE, a possible contribution of volatile compounds can be suggested, strengthening the hypothesis that the entire phytocomplex can contribute to the H. procumbens healing properties.

TAMM HORSFALL PROTEIN: THE MEN BEHIND THE EPONYM

2019 ◽  
Vol 23 (2) ◽  
pp. 117-119 ◽  
Author(s):  
D. N. Paskalev ◽  
B. T. Galunska ◽  
D. Petkova-Valkova
Keyword(s):  
Viral Replication ◽  
Research Team ◽  
Molecular Mechanisms ◽  
Thick Ascending Limb ◽  
Rockefeller Institute ◽  
The Usa ◽  
Natural Inhibitor ◽  
Simplex Virus ◽  
First Time ◽  
New Protein

Tamm–Horsfall Protein (uromodulin) is named after Igor Tamm and Franc Horsfall Jr who described it for the first time in 1952. It is a glycoprotein, secreted by the cells in the thick ascending limb of the loop of Henle. This protein will perform a number of important pathophysiological functions, including protection against uroinfections, especially caused by E. Сoli, and protection against formation of calcium concernments in the kidney. Igor Tamm (1922-1995) is an outstanding cytologist, virologist and biochemist. He is one of the pioneers in the study of viral replication. He was born in Estonia and died in the USA. In 1964 he was elected for a professorship in Rockefeller Institute for Medical Research, where has been working continuously. Since 1959, he became a head of the virology lab established by his mentor and co-author Franc Horsfall. In the course of studies on the natural inhibitor of viral replication, Tamm and Horsfall isolated and characterized biochemically a new protein named after their names. Franc Lappin Horsfall Jr (1906-1971) was a well-known clinician and virologist with remarkable achievements in internal medicine. He was born and died in the USA. He worked in the Rockefeller Hospital from 1934 to 1960, then in the Center for Cancer Research at the Sloan-Kettering Institute. Here he was a leader of a research team studying the molecular mechanisms of immunity, the effects of chemotherapy with benzimidazole compounds (together with I. Tamm), coxsackie viruses, herpes simplex virus, etc. 

scholarly journals Allelopathic Effect of Serphidium kaschgaricum (Krasch.) Poljak. Volatiles on Selected Species

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 495
Author(s):  
Shixing Zhou ◽  
Toshmatov Zokir ◽  
Yu Mei ◽  
Lijing Lei ◽  
Kai Shi ◽  
...  
Keyword(s):  
Volatile Compounds ◽  
Volatile Oil ◽  
Amaranthus Retroflexus ◽  
Allelopathic Effect ◽  
Chemical Profile ◽  
Volatile Oils ◽  
Phytotoxic Activity ◽  
Volatile Organic ◽  
First Time ◽  
Stem Leaf

The chemical profile and allelopathic effect of the volatile organic compounds (VOCs) produced by a dominant shrub Serphidium kaschgaricum (Krasch.) Poljak. growing in northwestern China was investigated for the first time. Serphidium kaschgaricu was found to release volatile compounds into the surroundings to affect other plants’ growth, with its VOCs suppressing root elongation of Amaranthus retroflexus L. and Poa annua L. by 65.47% and 60.37% at 10 g/1.5 L treatment, respectively. Meanwhile, volatile oils produced by stems, leaves, flowers and flowering shoots exhibited phytotoxic activity against A. retroflexus and P. annua. At 0.5 mg/mL, stem, leaf and flower oils significantly reduced seedling growth of the receiver plants, and 1.5 mg/mL oils nearly completely prohibited seed germination of both species. GC/MS analysis revealed that among the total 37 identified compounds in the oils, 19 of them were common, with eucalyptol (43.00%, 36.66%, 19.52%, and 38.68% in stem, leaf, flower and flowering shoot oils, respectively) and camphor (21.55%, 24.91%, 21.64%, and 23.35%, respectively) consistently being the dominant constituents in all oils. Eucalyptol, camphor and their mixture exhibited much weaker phytotoxicity compared with the volatile oils, implying that less abundant compounds in the volatile oil might contribute significantly to the oils’ activity. Our results suggested that S. kaschgaricum was capable of synthesizing and releasing allelopathic volatile compounds into the surroundings to affect neighboring plants’ growth, which might improve its competitiveness thus facilitate the establishment of dominance.

scholarly journals Phytochemical and Ethnopharmacological Perspectives of Ehretia laevis

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3489
Author(s):  
Pooja Sharma ◽  
Richa Shri ◽  
Fidele Ntie-Kang ◽  
Suresh Kumar
Keyword(s):  
Pentacyclic Triterpenoids ◽  
Diverse Range ◽  
Plant Parts ◽  
Tribal Communities ◽  
Crude Extracts ◽  
Traditional Remedy ◽  
Botanical Description ◽  
Pharmacological Screening ◽  
Therapeutic Activities ◽  
First Time

Ehretia laevis Roxb. (Boraginaceae) has been extensively used as a traditional remedy for the treatment of a diverse range of ailments related to the respiratory system, the gastrointestinal tract, the reproductive system, and against several infections. This review critically assesses and documents, for the first time, the fragmented information on E. laevis, including its botanical description, folklore uses, bioactive phyto metabolites and pharmacological activities. The goal is to explore this plant therapeutically. Ethnomedicinal surveys reveal that E. laevis has been used by tribal communities in Asian countries for the treatment of various disorders. Quantitative and qualitative phytochemical investigations of E. laevis showed the presence of important phytoconstituents such as pentacyclic triterpenoids, phenolic acids, flavonoids, fatty acids, steroids, alkaloids, aliphatic alcohols, hydrocarbons, amino acids, carbohydrates, vitamins and minerals. Fresh plant parts, crude extracts, fractions and isolated compounds have been reported to exhibit broad spectrum of therapeutic activities viz., antioxidant, antiarthritic, antidiabetic, anti-inflammatory, antiulcer, antidiarrheal, antidysenteric, wound healing and anti-infective activities. E. laevis is shown to be an excellent potential source of drugs for the mitigation of jaundice, asthma, dysentery, ulcers, diarrhea, ringworm, eczema, diabetes, fissure, syphilis, cuts and wounds, inflammation, liver problems, venereal and infectious disorders. Although few investigations authenticated its traditional uses but employed uncharacterized crude extracts of the plant, the major concerns raised are reproducibility of therapeutic efficacy and safety of plant material. The outcomes of limited pharmacological screening and reported bioactive compounds of E. laevis suggest that there is an urgent need for in-depth pharmacological investigations of the plant.

scholarly journals Combining QTL Mapping and Gene Expression Analysis to Elucidate the Genetic Control of ‘Crumbly’ Fruit in Red Raspberry (Rubus idaeus L.)

Agronomy ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 794
Author(s):  
Luca M. Scolari ◽  
Robert D. Hancock ◽  
Pete E. Hedley ◽  
Jenny Morris ◽  
Kay Smith ◽  
...  
Keyword(s):  
Genetic Control ◽  
Developmental Disorder ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Microarray Experiment ◽  
Rubus Idaeus ◽  
Red Raspberry ◽  
Genotype By Sequencing ◽  
First Time ◽  
Selection Of

‘Crumbly’ fruit is a developmental disorder in raspberry that results in malformed and unsaleable fruits. For the first time, we define two distinct crumbly phenotypes as part of this work. A consistent crumbly fruit phenotype affecting the majority of fruits every season, which we refer to as crumbly fruit disorder (CFD) and a second phenotype where symptoms vary across seasons as malformed fruit disorder (MFD). Here, segregation of crumbly fruit of the MFD phenotype was examined in a full-sib family and three QTL (Quantitative Trait Loci) were identified on a high density GbS (Genotype by Sequencing) linkage map. This included a new QTL and more accurate location of two previously identified QTLs. A microarray experiment using normal and crumbly fruit at three different developmental stages identified several genes that were differentially expressed between the crumbly and non-crumbly phenotypes within the three QTL. Analysis of gene function highlighted the importance of processes that compromise ovule fertilization as triggers of crumbly fruit. These candidate genes provided insights regarding the molecular mechanisms involved in the genetic control of crumbly fruit in red raspberry. This study will contribute to new breeding strategies and diagnostics through the selection of molecular markers associated with the crumbly trait.

scholarly journals Analysis of a Preliminary microRNA Expression Signature in a Human Telangiectatic Osteogenic Sarcoma Cancer Cell Line

2021 ◽  
Vol 22 (3) ◽  
pp. 1163
Author(s):  
Gaia Palmini ◽  
Cecilia Romagnoli ◽  
Simone Donati ◽  
Roberto Zonefrati ◽  
Gianna Galli ◽  
...  
Keyword(s):  
Cell Line ◽  
Molecular Mechanisms ◽  
Osteogenic Sarcoma ◽  
Cancer Cell Line ◽  
Microscopic Features ◽  
In Vitro Establishment ◽  
Profile Characteristic ◽  
First Time

Telangiectatic osteosarcoma (TOS) is an aggressive variant of osteosarcoma (OS) with distinctive radiographic, gross, microscopic features, and prognostic implications. Despite several studies on OS, we are still far from understanding the molecular mechanisms of TOS. In recent years, many studies have demonstrated not only that microRNAs (miRNAs) are involved in OS tumorigenesis, development, and metastasis, but also that the presence in high-grade types of OS of cancer stem cells (CSCs) plays an important role in tumor progression. Despite these findings, nothing has been described previously about the expression of miRNAs and the presence of CSCs in human TOS. Therefore, we have isolated/characterized a putative CSC cell line from human TOS (TOS-CSCs) and evaluated the expression levels of several miRNAs in TOS-CSCs using real-time quantitative assays. We show, for the first time, the existence of CSCs in human TOS, highlighting the in vitro establishment of this unique stabilized cell line and an identification of a preliminary expression of the miRNA profile, characteristic of TOS-CSCs. These findings represent an important step in the study of the biology of one of the most aggressive variants of OS and the role of miRNAs in TOS-CSC behavior.

scholarly journals COXIBs and 2,5-dimethylcelecoxib counteract the hyperactivated Wnt/β-catenin pathway and COX-2/PGE2/EP4 signaling in glioblastoma cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aleksandra Majchrzak-Celińska ◽  
Julia O. Misiorek ◽  
Nastassia Kruhlenia ◽  
Lukasz Przybyl ◽  
Robert Kleszcz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Methylation Status ◽  
Receptor Expression ◽  
Cell Cycle Distribution ◽  
Ep4 Receptor ◽  
Cox 2 ◽  
The Impact

Abstract Background Glioblastoma (GBM) is the deadliest and the most common primary brain tumor in adults. The invasiveness and proliferation of GBM cells can be decreased through the inhibition of Wnt/β-catenin pathway. In this regard, celecoxib is a promising agent, but other COXIBs and 2,5-dimethylcelecoxib (2,5-DMC) await elucidation. Thus, the aim of this study was to analyze the impact of celecoxib, 2,5-DMC, etori-, rofe-, and valdecoxib on GBM cell viability and the activity of Wnt/β-catenin pathway. In addition, the combination of the compounds with temozolomide (TMZ) was also evaluated. Cell cycle distribution and apoptosis, MGMT methylation level, COX-2 and PGE2 EP4 protein levels were also determined in order to better understand the molecular mechanisms exerted by these compounds and to find out which of them can serve best in GBM therapy. Methods Celecoxib, 2,5-DMC, etori-, rofe- and valdecoxib were evaluated using three commercially available and two patient-derived GBM cell lines. Cell viability was analyzed using MTT assay, whereas alterations in MGMT methylation level were determined using MS-HRM method. The impact of COXIBs, in the presence and absence of TMZ, on Wnt pathway was measured on the basis of the expression of β-catenin target genes. Cell cycle distribution and apoptosis analysis were performed using flow cytometry. COX-2 and PGE2 EP4 receptor expression were evaluated using Western blot analysis. Results Wnt/β-catenin pathway was attenuated by COXIBs and 2,5-DMC irrespective of the COX-2 expression profile of the treated cells, their MGMT methylation status, or radio/chemoresistance. Celecoxib and 2,5-DMC were the most cytotoxic. Cell cycle distribution was altered, and apoptosis was induced after the treatment with celecoxib, 2,5-DMC, etori- and valdecoxib in T98G cell line. COXIBs and 2,5-DMC did not influence MGMT methylation status, but inhibited COX-2/PGE2/EP4 pathway. Conclusions Not only celecoxib, but also 2,5-DMC, etori-, rofe- and valdecoxib should be further investigated as potential good anti-GBM therapeutics.

Vasculoprotective effects of ginger (Zingiber officinale Roscoe) and underlying molecular mechanisms

2021 ◽  
Author(s):  
Chao Li ◽  
Jie Li ◽  
Feng Jiang ◽  
Nikolay T. Tzvetkov ◽  
Jaroslaw O. Horbanczuk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Molecular Mechanisms ◽  
Zingiber Officinale ◽  
Protective Effects ◽  
Bioactive Constituents ◽  
Zingiber Officinale Roscoe

Bioactive constituents of ginger are reviewed. Vascular protective effects of ginger and a variety of mechanisms are presented. Ginger and its components show vasculoprotective effects in clinical trials.

The development of the human uterus: morphogenesis to menarche

2020 ◽  
Vol 27 (1) ◽  
pp. 1-26
Author(s):  
Marwan Habiba ◽  
Rosemarie Heyn ◽  
Paola Bianchi ◽  
Ivo Brosens ◽  
Giuseppe Benagiano
Keyword(s):  
Molecular Mechanisms ◽  
Uterine Bleeding ◽  
Molecular Techniques ◽  
Receptor Expression ◽  
Abnormal Development ◽  
Uterine Disease ◽  
Adult Onset ◽  
Uterine Anomalies ◽  
Mullerian Ducts ◽  
Uterine Development

ABSTRACT There is emerging evidence that early uterine development in humans is an important determinant of conditions such as ontogenetic progesterone resistance, menstrual preconditioning, defective deep placentation and pre-eclampsia in young adolescents. A key observation is the relative infrequency of neonatal uterine bleeding and hormone withdrawal at birth. The origin of the uterus from the fusion of the two paramesonephric, or Müllerian, ducts was described almost 200 years ago. The uterus forms around the 10th week of foetal life. The uterine corpus and the cervix react differently to the circulating steroid hormones during pregnancy. Adult uterine proportions are not attained until after puberty. It is unclear if the endometrial microbiome and immune response—which are areas of growing interest in the adult—play a role in the early stages of uterine development. The aim is to review the phases of uterine development up until the onset of puberty in order to trace the origin of abnormal development and to assess current knowledge for features that may be linked to conditions encountered later in life. The narrative review incorporates literature searches of Medline, PubMed and Scopus using the broad terms individually and then in combination: uterus, development, anatomy, microscopy, embryology, foetus, (pre)-puberty, menarche, microbiome and immune cells. Identified articles were assessed manually for relevance, any linked articles and historical textbooks. We included some animal studies of molecular mechanisms. There are competing theories about the contributions of the Müllerian and Wolffian ducts to the developing uterus. Endometrium features are suggestive of an oestrogen effect at 16–20 weeks gestation. The discrepancy in the reported expression of oestrogen receptor is likely to be related to the higher sensitivity of more recent techniques. Primitive endometrial glands appear around 20 weeks. Features of progestogen action are expressed late in the third trimester. Interestingly, progesterone receptor expression is higher at mid-gestation than at birth when features of endometrial maturation are rare. Neonatal uterine bleeding occurs in around 5% of neonates. Myometrial differentiation progresses from the mesenchyme surrounding the endometrium at the level of the cervix. During infancy, the uterus and endometrium remain inactive. The beginning of uterine growth precedes the onset of puberty and continues for several years after menarche. Uterine anomalies may result from fusion defects or atresia of one or both Müllerian ducts. Organogenetic differentiation of Müllerian epithelium to form the endometrial and endocervical epithelium may be independent of circulating steroids. A number of genes have been identified that are involved in endometrial and myometrial differentiation although gene mutations have not been demonstrated to be common in cases of uterine malformation. The role, if any, of the microbiome in relation to uterine development remains speculative. Modern molecular techniques applied to rodent models have enhanced our understanding of uterine molecular mechanisms and their interactions. However, little is known about functional correlates or features with relevance to adult onset of uterine disease in humans. Prepubertal growth and development lends itself to non-invasive diagnostics such as ultrasound and MRI. Increased awareness of the occurrence of neonatal uterine bleeding and of the potential impact on adult onset disease may stimulate renewed research in this area.

scholarly journals A Central Role for the Armadillo Protein Plakoglobin in the Autoimmune Disease Pemphigus Vulgaris

2001 ◽  
Vol 153 (4) ◽  
pp. 823-834 ◽  
Author(s):  
Reto Caldelari ◽  
Alain de Bruin ◽  
Dominique Baumann ◽  
Maja M. Suter ◽  
Christiane Bierkamp ◽  
...  
Keyword(s):  
Steric Hindrance ◽  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Pemphigus Vulgaris ◽  
Cell Types ◽  
Linear Distribution ◽  
Igg Binding ◽  
Vitro Model ◽  
First Time

In pemphigus vulgaris (PV), autoantibody binding to desmoglein (Dsg) 3 induces loss of intercellular adhesion in skin and mucous membranes. Two hypotheses are currently favored to explain the underlying molecular mechanisms: (a) disruption of adhesion through steric hindrance, and (b) interference of desmosomal cadherin-bound antibody with intracellular events, which we speculated to involve plakoglobin. To investigate the second hypothesis we established keratinocyte cultures from plakoglobin knockout (PG−/−) embryos and PG+/+ control mice. Although both cell types exhibited desmosomal cadherin-mediated adhesion during calcium-induced differentiation and bound PV immunoglobin (IgG) at their cell surface, only PG+/+ keratinocytes responded with keratin retraction and loss of adhesion. When full-length plakoglobin was reintroduced into PG−/− cells, responsiveness to PV IgG was restored. Moreover, in these cells like in PG+/+ keratinocytes, PV IgG binding severely affected the linear distribution of plakoglobin at the plasma membrane. Taken together, the establishment of an in vitro model using PG+/+ and PG−/− keratinocytes allowed us (a) to exclude the steric hindrance only hypothesis, and (b) to demonstrate for the first time that plakoglobin plays a central role in PV, a finding that will provide a novel direction for investigations of the molecular mechanisms leading to PV, and on the function of plakoglobin in differentiating keratinocytes.

scholarly journals Chemical Constituents of Eupatorium japonicum and Anti-Inflammatory, Cytotoxic, and Apoptotic Activities of Eupatoriopicrin on Cancer Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Minh Giang Phan ◽  
Thi Thao Do ◽  
Thi Nga Nguyen ◽  
Thi Viet Huong Do ◽  
Ngoc Phuc Dong ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Activities ◽  
Chemical Constituents ◽  
Sesquiterpene Lactones ◽  
No Production ◽  
Bioactive Constituents ◽  
Anti Inflammatory ◽  
First Time ◽  
Eupatorium Japonicum

Eupatorium japonicum Thunb. of the plant family Asteraceae is a popular traditional herb in Vietnam. However, its chemical constituents as well as bioactive principles have not been investigated yet. We investigated the phytochemistry of E. japonicum in Vietnam and isolated seventeen compounds (1–17) including phytosterols, terpenoids, phenolic acids, flavonoids, fatty alcohols, and fatty acids. They were structurally determined by MS and NMR analysis. Except for compounds 6 and 12, all the other compounds were identified for the first time from E. japonicum. Since many sesquiterpene lactones with α-methylene γ-lactone ring are reported as anti-inflammatory and anticancer agents, eupatoriopicrin (10), 1-hydroxy-8-(4,5-dihydroxytigloyloxy)eudesma-4(15),11(13)-dien-6,12-olide (11) were selected among the isolates for biological assays. Compound 10 was identified as the main bioactive sesquiterpene lactone of E. japonicum showing its potent anti-inflammatory and cytotoxic activity through inhibiting NO production and the growth of HepG2 and MCF-7 human cancer cell lines. For the first time, eupatoriopicrin (10) was demonstrated to strongly inhibit NTERA-2 human cancer stem cell (CSC) line in vitro. It is noticeable that the cytotoxicity of eupatoriopicrin against NTERA-2 cells is mediated by its apoptosis-inducing capability of 10 as demonstrated by the results of Hoechst 33342 staining, flow cytometry apoptosis analysis, and caspase-3 activity assays. The biological activities of the main bioactive constituents 1–7, 10, 12, and 15 supported the reported anti-inflammatory and anticancer properties of extracts from E. japonicum.

Sign in / Sign up

Export Citation Format

Share Document