scholarly journals Fractional Deletion Of Compound Kushen Injection, A Natural Compound Mixture, Indicates Cytokine Signaling Pathways Are Critical For Its Perturbation Of The Cell Cycle

2018 ◽  
Author(s):  
TN Aung ◽  
S Nourmohammadi ◽  
Z Qu ◽  
Y Harata-Lee ◽  
J Cui ◽  
...  

AbstractWe have used computational and experimental biology approaches to identify candidate mechanisms of action of a traditional Chinese medicine. Compound Kushen Injection (CKI), in a breast cancer cell line in which CKI causes apoptosis. Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatography (HPLC) fractionation and reconstitution approach to define chemical fractions required for CKI to induce apoptosis in MDA-MB-231 cells. Our initial fractionation separated major from minor compounds, and showed that the major compounds accounted for little of the activity of CKI. By systematically perturbing the major compounds in CKI we found that removal of no single major compound could alter the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical compounds with respect to CKI activity. We then used RNA sequencing and transcriptome analysis to correlate compound removal with gene expression and phenotype data. We determined that many compounds in CKI are required for its effectiveness in triggering apoptosis but that significant modulation of its activity is conferred by a small number of compounds. In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
T. N. Aung ◽  
S. Nourmohammadi ◽  
Z. Qu ◽  
Y. Harata-Lee ◽  
J. Cui ◽  
...  

Abstract We used computational and experimental biology approaches to identify candidate mechanisms of action of aTraditional Chinese Medicine, Compound Kushen Injection (CKI), in a breast cancer cell line (MDA-MB-231). Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatography (HPLC) fractionation and reconstitution approach to define chemical fractions required for CKI to induce apoptosis. The initial fractionation separated major from minor compounds, and it showed that major compounds accounted for little of the activity of CKI. Furthermore, removal of no single major compound altered the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical with respect to CKI activity. Transcriptome analysis was used to correlate compound removal with gene expression and phenotype data. Many compounds in CKI are required to trigger apoptosis but significant modulation of its activity is conferred by a small number of compounds. In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets.


Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2887
Author(s):  
Kena Li ◽  
Jens Prothmann ◽  
Margareta Sandahl ◽  
Sara Blomberg ◽  
Charlotta Turner ◽  
...  

Base-catalyzed depolymerization of black liquor retentate (BLR) from the kraft pulping process, followed by ultrafiltration, has been suggested as a means of obtaining low-molecular-weight (LMW) compounds. The chemical complexity of BLR, which consists of a mixture of softwood and hardwood lignin that has undergone several kinds of treatment, leads to a complex mixture of LMW compounds, making the separation of components for the formation of value-added chemicals more difficult. Identifying the phenolic compounds in the LMW fractions obtained under different depolymerization conditions is essential for the upgrading process. In this study, a state-of-the-art nontargeted analysis method using ultra-high-performance supercritical fluid chromatography coupled to high-resolution multiple-stage tandem mass spectrometry (UHPSFC/HRMSn) combined with a Kendrick mass defect-based classification model was applied to analyze the monomers and oligomers in the LMW fractions separated from BLR samples depolymerized at 170–210 °C. The most common phenolic compound types were dimers, followed by monomers. A second round of depolymerization yielded low amounts of monomers and dimers, while a high number of trimers were formed, thought to be the result of repolymerization.


2016 ◽  
Vol 37 (4) ◽  
pp. 1857 ◽  
Author(s):  
Sidiane Coltro-Roncato ◽  
José Renato Stangarlin ◽  
Affonso Celso Gonçalves Jr. ◽  
Odair José Kuhn ◽  
Edilaine Della Valentina Gonçalves ◽  
...  

Alternative methods for the control of nematodes, such as the use of plant secondary metabolites, can be explored for integrated pest management systems. The objective of this work was to assess the best solvent for obtaining allyl isothiocyanate from Crambe abyssinica leaves, and the effects of this extract on Meloidogyne incognita and M. javanica. Dry leaves of C. abyssinica at 200 mg L-1 were used to prepare extracts by using water (by infusion and grinding), acetone, water + ethanol (hydroalcoholic extraction), methanol, hexane, and chloroform as solvents. Following the evaporation of the solvents, the residue was resuspended in water for use in the experiments. Distilled water and chemical nematicide were used as control treatments. Once the most effective extracts were defined, the following dosages of dried crambe leaves were used: 0, 200, 300, 400, and 500 mg L-1. High performance liquid chromatography (HPLC) was used to quantify the allyl isothiocyanate present in the extracts. After the solvents evaporated, the residues were eluted with water and used in assays with 200 eggs for the hatching test or 200 second stage juveniles (J2) for mobility and mortality tests. The hydroalcoholic extract was the most effective in reducing the hatching of M. incognita and M. javanica juveniles, by 71.6 and 74.4 percentage points, respectively. The mortality of M. incognita and M. javanica in the hydroalcoholic extract was 93.2 and 64.4%, respectively, followed by the methanol extract (17.6 and 34%) and the extract obtained by grinding (9.2 and 28%). The hydroalcoholic extract at 250 mg L-1 showed high nematicidal effect. The HPLC analysis of the extracts revealed that only the methanol and hydroalcoholic extracts had allyl isothiocyanate, indicating that the inhibitory effects on the hatching, mobility, and mortality were not solely attributed to the presence of this compound.


2011 ◽  
Vol 6 (4) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Botond Borcsa ◽  
Dezső Csupor ◽  
Peter Forgo ◽  
Ute Widowitz ◽  
Rudolf Bauer ◽  
...  

The term lipo-alkaloid is used for C19 aconitane alkaloids containing one or two long-chain fatty acid residues. Lipo-alkaloids are transesterified derivatives of the most toxic and highly effective diester-type diterpene alkaloids, such as aconitine, hypaconitine, mesaconitine. Lipo-alkaloids are native minor compounds of aconite drugs, but their amount significantly increases after traditional processing, which is a general method in the Far Eastern traditional medicinal systems. Analytical works demonstrated that cautious processing (usually boiling) of crude aconite roots decreases the amount of normal diterpene alkaloids and increases the concentration of lipo-alkaloids resulting in the reduction of toxicity of the drugs. Many papers reported that lipo-alkaloids occur as a complex mixture in the drugs, and the isolation of the individual components is extremely difficult. These compounds have been identified using highly sensitive analytical methods (HPLC-MS, NMR), and semisynthetic approaches have been developed to ensure lipo-alkaloids in pure form for pharmacological studies. This review summarizes the structure, chemistry, semisynthesis, analytics and bioactivities of lipo-alkaloids. On the basis of 32 references this is the first comprehensive study on this topic, covering the data of 173 compounds.


Plants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 879
Author(s):  
Petra Lovecká ◽  
Alžběta Svobodová ◽  
Anna Macůrková ◽  
Blanka Vrchotová ◽  
Kateřina Demnerová ◽  
...  

Magnolia plants are used both as food supplements and as cosmetic and medicinal products. The objectives of this work consisted of preparing extracts from leaves and flowers of eight Magnolia plants, and of determining concentrations of magnolol (1 to 100 mg·g−1), honokiol (0.11 to 250 mg·g−1), and obovatol (0.09 to 650 mg·g−1), typical neolignans for the genus Magnolia, in extracts made by using a methanol/water (80/20) mixture. The tested Magnolia plants, over sixty years old, were obtained from Průhonický Park (Prague area, Czech Republic): M. tripetala MTR 1531, M. obovata MOB 1511, and six hybrid plants Magnolia × pruhoniciana, results of a crossbreeding of M. tripetala MTR 1531 with M. obovata MOB 1511. The identification of neolignans was performed by HRMS after a reversed-phase high-performance liquid chromatography (RP-HPLC) fractionation of an extract from M. tripetala MTR 1531. The highest concentrations of neolignans were found in the flowers, most often in their reproductive parts, and obovatol was the most abundant in every tested plant. The highest concentrations of neolignans were detected in parent plants, and lower concentrations in hybrid magnolias. Flower extracts from the parent plants M. tripetala MTR 1531 and M. obovata MOB 1511, flower extracts from the hybrid plants Magnolia × pruhoniciana MPR 0271, MPR 0151, and MPR 1531, and leaf extract from the hybrid plant Magnolia × pruhoniciana MPR 0271 inhibited growth of Staphylococcus aureus.


2011 ◽  
Vol 38 (9) ◽  
pp. 682 ◽  
Author(s):  
Jean Popovici ◽  
Vincent Walker ◽  
Cédric Bertrand ◽  
Floriant Bellvert ◽  
Maria P. Fernandez ◽  
...  

Plant secondary metabolites play an important role in the interaction between plants and their environment. For example, mutualistic nitrogen-fixing symbioses typically involve phenolic-based recognition between host plants and bacteria. Although these mechanisms are well studied in the rhizobia–legume symbiosis, little is known about the role of plant phenolics in the symbiosis between actinorhizal plants and the actinobacterium Frankia. In this study, the responsiveness of two Myricaceae plant species, Myrica gale L. and Morella cerifera L., to Frankia inoculation was correlated with the plant–bacteria compatibility status. Two Frankia strains were inoculated: ACN14a, compatible with both M. gale and M. cerifera and Ea112, compatible only with M. cerifera. The effect of inoculation on root phenolic metabolism was evaluated by metabolic profiling based on high-performance liquid chromatography (HPLC) and principal component analysis (PCA). Our results revealed that: (i) both Frankia strains induced major modifications in root phenolic content of the two Myricaceae species and (ii) strain-dependant modifications of the phenolic contents were detected. The main plant compounds differentially affected by Frankia inoculation are phenols, flavonoids and hydroxycinnamic acids. This work provides evidence that during the initial phases of symbiotic interactions, Myricaceae plants adapt their secondary metabolism in accordance with the compatibility status of Frankia bacterial strains.


2016 ◽  
Vol 11 (4) ◽  
pp. 844 ◽  
Author(s):  
Vivek K. Bajpai ◽  
Rajib Majumder ◽  
Jae Gyu Park

<p>Chromatographic techniques have significant role in natural products chemistry as well as contribute dramatically in the discovery of novel and innovative compounds of pharmaceutical and biomedical importance. This study focused on step-by-step visual demonstration of fractionation and isolation of biologically active plant secondary metabolites using column-chromatographic techniques. Isolation of bioactive compounds using column-chromatographic involves: a) Preparation of sample; b) Packing of column; c) Pouring of sample into the column; d) Elution of fractions; and e) Analysis of each fractions using thin layer chromatography. However, depending on nature of research, compounds can be further purified using high performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) spectral analyses.</p><p><strong>Video Clips</strong></p><p><a href="https://www.youtube.com/v/pr8mrBoI8xA">Part 1:</a> 3 min 45 sec</p><p><a href="https://www.youtube.com/v/rYrfClKn-og">Part 2:</a> 6 min 21 sec</p><p><a href="https://www.youtube.com/v/kffHXxuPwbo">Part 3</a>: 4 min 45 sec</p>


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Amita Mishra ◽  
Shashank Kumar ◽  
Abhay K. Pandey

Present communication reports the scientific evaluation ofTinospora cordifoliafor its medicinal efficacy which includes phytochemical screening, antimicrobial, antioxidant, and anticancer activities of the plant. Secondary metabolites including anthraquinones, terpenoids, and saponins were present in many extracts in addition to phenolics. Total phenol contents in various extracts were found in the range of 8.75–52.50 catechol equivalent per gram (CE/g). In disc diffusion assays, polar extracts exhibited considerable inhibition againstKlebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains ofE. coli,Pseudomonasspp., andProteusspp. Minimum bactericidal concentration (MBC) values of potential extracts were found between 1.29 and 22.73 mg/mL. The lowest MBC (1.29 mg/mL) was recorded for acetone and ethyl acetate extracts againstK. pneumoniaeandPseudomonasspp., respectively. The antioxidant activity of the extracts was comparable to that of standard antioxidants and concentration-dependent response was shown in reducing power assay. Aqueous extracts demonstrated substantial metal ion chelating activity (67–95%) at lower concentrations (10–40 μg/mL). Other extracts also exhibited considerable metal chelating response. Most of the extracts revealed considerable inhibition of MCF-7 cancer cell line. The study established remarkable antibacterial, antioxidant, and anticancer potential inT. cordifoliastem extracts.


Biologia ◽  
2015 ◽  
Vol 70 (1) ◽  
Author(s):  
Saurabh Dubey ◽  
Ketki Patil ◽  
Pooja Sharma ◽  
Ghanshyam D. Tandon

AbstractThere is an urgent need to discover new anti-microbial agents that can overcome the increasing antibiotic resistance posed by multidrug resistant, β-lactamase producing bacteria. β-Lactam antibiotics are structurally related through the presence of a core β-lactam ring. Resistant pathogens are able to produce β-lactamase enzymes that hydrolyze the β-lactam ring and inactivate the antibiotic. One approach to counteract this resistance is to develop β-lactamase inhibitors, which, on administration with β-lactams, restores the antibiotic activity for its continued clinical use. In the present study, a fungal Penicillium strain was isolated, identified and characterized for its antimicrobial and β-lactamase inhibition activities. The strain was identified as Penicillium piceum and was grown in suitable media under submerged cultivation. The antibacterial activity was observed against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Higher antimicrobial activity was observed against gram-positive bacteria as compared to gram-negative bacteria. A certain amount of antifungal activity was also observed against the fungal strains of Penicilium chrysogenum, Rhizopus stolonifer, Fusarium moniliforme, Aspergillus niger, Giberella fujikuroi and Saccharomyces cerevisiae. Iodometric and bioassay analyses confirmed that P. piceum produced β-lactamase inhibitors having activity against penicillinase (Bacillus cereus). Solvent-solvent extraction with butanol yielded a three-fold increase in β-lactamase inhibition activity. High-performance liquid chromatography analysis of the concentrated product proved it to be a single compound. The infrared (IR) spectrum of the compound was compared with the reference IR spectra of sulbactam sodium, tazobactam and potassium clavulanate. It was found to be different thereby inferring the need for extensive structural elucidation for future applications.


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