Metabolic and pharmacological profiling of Penicillium claviforme by a combination of experimental and bioinformatic approaches

BackgroundPenicillium produces a wide range of structurally diverse metabolites with significant pharmacological impacts in medicine and agriculture. For the first time, a complete metabolome of Penicillium claviforme (P. claviforme) (FBP-DNA-1205) was studied alongside pharmacological research in this study.MethodsThe metabolic profile of P. claviforme fermented on Potato Dextrose Broth (PDB) was investigated in this work. The complete metabolomics studies of fungus were performed using GC-MS and LC-MS-QTOF techniques. An in vitro model was utilised to study the cytotoxic and antioxidant activities, while an in vivo model was employed to investigate the antinociceptive and acute toxicity activities. Molecular Operating Environment (MOE) software was used for molecular docking analysis.ResultsGC-MS study showed the presence of alkanes, fatty acids, esters, azo and alcoholic compounds. Maculosin, obtain, phalluside, quinoline, 4,4’-diaminostilbene, funaltrexamine, amobarbital, and fraxetin were among the secondary metabolites identified using the LC-MS-QTOF technique. The n-hexane fraction of P. claviforme displayed significant cytotoxic activity in vitro, with an LD50 value of 92.22 µgml⁻¹. The antinociceptive effects in vivo were dose-dependent significantly (p < .001). Interestingly, during the 72 h of investigation, no acute toxicity was demonstrated. In addition, a docking study of tentatively identified metabolites against the inflammatory enzyme (COX-2) supported the antinociceptive effect in an in silico model.ConclusionMetabolic profile of P. claviforme shows the presence of biologically relevant compounds in ethyl acetate extract. In addition, P. claviforme exhibits substantial antioxidant and cytotoxic activities in an in vitro model as well as antinociceptive activity in an in vivo model. The antinociceptive action is also supported by a molecular docking study. This research has opened up new possibilities in the disciplines of mycology, agriculture, and pharmaceutics.

Key messages

• The first time explored complete metabolome through GC-MS and LC-MS-QTOF.
• Both in vivo & in vitro pharmacological investigation of P. claviforme.
• In silico molecular docking of LC-MS-QTOF metabolites.

     

Antidiabetic effect of alcoholic extract of Caralluma sinaica L. on streptozotocin-induced diabetic rabbits

People of Asir region of Saudi Arabia chew Caralluma sinaica (CS) to lower glucose level. To establish its utility in diabetes mellitus we have under taken this study. The effect of CS on streptozotocin (STZ)-induced diabetic model as well as effect on oral glucose tolerance test were studied. The extract was shown to have positive test for possessing following chemical constituents like phenolic alkaloids, glycosides, flavonoids, coumarins, steroids and tannins. Administration of CS in different doses (50, 100, 150 and 200mg/kg, p.o.) to normal animals caused significant (P<0.01) decrease in glucose level. Prior administration of either CS (100mg/kg, p.o.) or glibenclamide (GB) (5mg/kg, p.o.) blocked the rise of glucose caused by the streptozotocin. Antidiabetic activity of CS was compared with clinically available drug GB. Administration of CS (100mg/kg, p.o.) to diabetic rabbits for 30 days has been shown to decrease plasma glucose level to almost normal level (P<0.001). Liver and kidney weight expressed as percentage of body weight significantly (P<0.05; P<0.01) increased in diabetic rabbits versus normal control (CNT). CS significantly (P<0.05) reversed the increasing weight of liver caused by STZ but not GB. STZ induced lowering of glycogen content of liver and muscle was reversed by both CS and GB. STZ induced a significant (P<0.001) increase in renal glycogen content this was almost normalized by CS (P<0.001) whereas GB significantly decreased (P<0.002) glycogen content. In oral glucose tolerance test administration of glucose increased plasma glucose level significantly in the diabetic control over the 2-h period. Compared to diabetic control plasma glucose levels in rabbits given CS or GB were significantly lower at all the time points that blood was sampled after oral glucose load. Comparing with the GB treatment blood glucose lowering effect was more pronounced for diabetic rabbits given CS. All these effects could explain the basis for use of this plant extract to manage diabetes mellitus.     

Soluble receptor for advanced glycation end products (sRAGE) and endogenous secretory RAGE (esRAGE) in amniotic fluid: modulation by infection and inflammation

Abstract Objective: The receptor for advanced glycation end products (RAGE) has been proposed to participate in the innate and adaptive immune responses. RAGE can induce production of pro-inflammatory cytokines and chemokines, as well as neutrophil chemotaxis in a manner that may be suppressed or stimulated by soluble, truncated forms of RAGE including the soluble form of RAGE (sRAGE) and endogenous secretory RAGE (esRAGE). The objective of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in the amniotic fluid concentration of sRAGE and esRAGE. Study design: Amniotic fluid (AF) was retrieved from patients in the following groups: 1) mid-trimester (14-18 weeks of gestation; n=68); 2) term not in labor (n=24); 3) term in labor (n=51); 4) preterm labor and intact membranes (n=124); and 5) preterm PROM (n=80). Intra-amniotic infection and inflammation were defined as the presence of a positive amniotic fluid culture for microorganisms and an AF interleukin-6 concentration >/=2.6 ng/mL, respectively. The AF concentration of sRAGE and esRAGE were determined using specific and sensitive ELISAs which measured total immunoreactive sRAGE and esRAGE, respectively. Patients were matched for gestational age at amniocentesis to compare the AF concentration of sRAGE and esRAGE in patients with and without IAI. Non-parametric statistics were used for analysis and a P<0.05 was considered significant. Results: 1) Patients at term not in labor had higher median AF concentrations of sRAGE and esRAGE than those in the mid-trimester (P<0.001 for both comparisons) and those at term in labor (P=0.03 and P=0.04, respectively); 2) patients with preterm labor and intact membranes with intra-amniotic infection/inflammation (IAI) had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.02 and P=0.005, respectively); 3) similarly, patients with preterm PROM with IAI had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.03 and P=0.02, respectively). Conclusion: Intra-amniotic infection/inflammation is associated with increased amniotic fluid concentrations of sRAGE and esRAGE. Changes in the amniotic fluid concentration of sRAGE and esRAGE may represent part of the immune response to intra-amniotic infection/inflammation.     

Recurrent preterm birth

Recurrent preterm birth is frequently defined as two or more deliveries before 37 completed weeks of gestation. The recurrence rate varies as a function of the antecedent for preterm birth: spontaneous versus indicated. Spontaneous preterm birth is the result of either preterm labor with intact membranes or preterm prelabor rupture of the membranes. This article reviews the body of literature describing the risk of recurrence of spontaneous and indicated preterm birth. Also discussed are the factors which modify the risk for recurrent spontaneous preterm birth (a short sonographic cervical length and a positive cervicovaginal fetal fibronectin test). Patients with a history of an indicated preterm birth are at risk not only for recurrence of this subtype, but also for spontaneous preterm birth. Individuals of black origin have a higher rate of recurrent preterm birth.     

Plasma adiponectin concentrations in non-pregnant, normal and overweight pregnant women

AIMS: Adiponectin is an adipokine that has anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic properties. This hormone has been implicated in both the physiological adaptation to normal pregnancy and in obstetrical complications. The aims of this study were to determine normal maternal plasma concentrations of adiponectin throughout gestation and to explore the relationships between plasma adiponectin concentration, pregnancy, and maternal overweight. METHODS: A cross-sectional study was designed to include normal pregnant (normal weight and overweight; 11-42 weeks of gestation), and non-pregnant women. Plasma adiponectin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. RESULTS: (1) Adiponectin was detectable in the plasma of all patients; (2) there was no significant differences in the median adiponectin concentration between pregnant and non-pregnant women; (3) plasma adiponectin concentrations were negatively correlated with gestational age only among normal weight pregnant women; and (4) overweight patients had significantly lower plasma adiponectin concentrations than normal weight women. CONCLUSIONS: Consistent with the increased insulin resistance and weight gain that occur in pregnancy, adiponectin concentrations were negatively correlated with gestational age. The results of this study and the nomogram herein presented, can serve as the basis to explore the relationship between adiponectin and pregnancy complications and facilitate the clinical use of this important adipokine.     

槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分（英文）

目的：研究槟榔子（Areca catechu）粗提取物中所含的抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分及其作用机制。方法：使用70%甲醇水溶液对槟榔子进行粗提取。使用生物发光血小板凝集仪在富血小板血浆中测定槟榔子粗提取物的抗血小板聚集作用,使用分光光度计在试管内测定槟榔子粗提取物对乙酰胆碱酯酶活性的抑制作用。检测槟榔子中的多种化合物以测定槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分。结果：槟榔子粗提取物能够抑制花生四烯酸、二磷酸腺苷、血小板活化因子、肾上腺素及钙离子载体引起的血小板聚集,尤其对二磷酸腺苷及钙离子载体引起的血小板聚集的抑制最为明显;槟榔子粗提取物能够显著抑制乙酰胆碱酯酶的活性。在所检测的槟榔子所含化合物中,只有儿茶素对肾上腺素引起的血小板聚集有显著的抑制作用,而这种抑制作用显著弱于槟榔子粗提取物,提示槟榔子中的其他成分参与了这种抑制作用;鞣酸、没食子酸、薯蓣皂苷元和异去甲槟榔次碱能够抑制乙酰胆碱酯酶的活性,其中鞣酸的抑制作用强于槟榔子粗提取物。结论：槟榔子中含有抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分,而发挥这些功效的确切成分有待进一步的研究证实。