Thymol derivatives with antibacterial and cytotoxic activity from the aerial parts of Ageratina adenophora

Three new thymol derivatives, 7-formyl-9-isobutyryloxy-8-hydroxythymol (1), 7,9-di-isobutyryloxy-8,10-dehydrothymol (2) and 2α-methoxyl-3β-methyl-6-methylol-2,3-dihydrobenzofuran (3), along with five known ones (4–8), were isolated from the aerial parts of the invasive plant Ageratina adenophora. Their structures were elucidated by extensive spectroscopic analysis and they were all isolated from the aerial part of A. adenophora for the first time. These compounds, except 8, selectively showed in vitro antimicrobial activity against three Gram-(+) and two Gram-(−) bacterial strains. In particular, compounds 1 and 5 showed notable in vitro antimicrobial activity against all five bacterial strains with IC₅₀ values ranging from 3.9 to 15.6 μg mL⁻¹, as compared to reference compound kanamycin sulfate with a MIC value 1.9–3.9 μg mL⁻¹. Compounds 1 and 5 were further revealed to show in vitro cytotoxic activity against three tested human tumor (MCF-7, NCI-H460 and HeLa) cell lines, with IC₅₀ values ranging from 7.45 to 28.63 μM. Compounds 7 and 8 selectively showed slight but detectable in vitro cytotoxicity toward MCF-7 and NCI-H460 cell lines, with IC₅₀ values 44.65–83.19 μM. No cytotoxic effects were detected in the bioassay of the other four thymol derivatives. The present results provide new data to support that the aerial parts of A. adenophora are a rich source of bioactive chemicals valuable in medicinal applications.

Eight thymol derivatives including three new ones (1–3) were obtained from the aerial parts of Ageratina adenophora, with most of them, in particular 1 and 5, showing notable in vitro antimicrobial and cytotoxic activity.     

Chemical composition of the volatile oil of Ageratum conyzoides aerial parts

The chemical components of the volatile oil of the aerial parts of Ageratum conyzoides obtained by hydrodistillation was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Forty six compounds accounting for 97.60% of the oil were identified. The main compounds were found to be ageratochromene (32.9%), 6-methoxyquinoline-1-oxide (20.77%), β-caryophyllene (19.79%), β-sinenesal (5.82%), β-sesquiphelandrene (1.99%) and τ-cadinene (1.44%). Ageratochromene, 6-methoxyquinoline-1-oxide, β-caryophyllene, β-sinensal, β-sesquiphellandrene and τ-cadinene were identified as major constituents in the oil for the first time.     

Cannabis: the evidence.

There has been a lot of publicity over the past year on the issue of whether the legal status of cannabis should be changed. Much of the debate has been emotional in nature. The aim of this article is to review the literature and to come to some conclusions based on sound scientific rationale and empirical studies.     

Geoclimatic influences on the constituents and antioxidant activity of extracts from the fruit of Arbutus unedo L.

We made a comparison between the total phenolic content, concentrations of flavonoids and antioxidant activity of four different extracts (1-butanol, ethyl acetate, chloroform, water) of Arbutus unedo L. fruit (Ericacea) of El Marsa and Terni area. The total phenolic content in the extracts was determined using the Folin-Ciocalteu reagent and it ranged between 26.57 and 48.23 gallic acid equivalents mg/g of dry weight of extract. The concentrations of flavonoids in plant extracts varied from 17.98 to 56.84 catechin equivalents mg/g. The antioxidant activity was analyzed in vitro using the DPPH reagent; among all extracts, ethyl acetate fraction from El Marsa area showed the highest antioxidant activity.     

三种赣产葛地上部分总黄酮提取工艺优化及含量测定

目的：比较三种赣产葛根及其地上部分中总黄酮的含量,采用正交试验得到葛地上部分总黄酮提取的最佳工艺条件。方法：以葛根素为对照品,采用紫外-可见分光光度法测定三种赣产葛根、茎、叶和花中总黄酮的含量,以乙醇浓度、料液比和提取时间为考察因素,通过正交法确定葛地上部分总黄酮的最佳提取工艺。结果：不同基源的葛及其地上部分总黄酮含量差异较大,经正交试验考察,得最佳提取工艺为：乙醇浓度60%、料液比1:50、回流提取1.5 h。结论：该含量测定方法操作简单、快速、准确,可用于葛不同部位总黄酮含量的同时测定。总黄酮提取工艺参数的优化将为葛地上部分资源的开发利用提供理论基础和科学依据。     

Acute and sub-acute toxicities of hydroalcoholic extract of Allium affine aerial parts in rats

Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,animals orally received the limit test dose of 2000 mg/kg of A.affine extract and were observed for 2 weeks.For sub-acute toxicity study,rats were orally treated with 125,250,and 500 mg/kg/day of the extract over 28 days,and hematological,biochemical,and histological evaluations were then conducted.Results:All rats were alive with normal body weight gain over 14 days,with LD50˃2000 mg/kg.No abnormality in body weight changes but significant increases in the relative weight of spleen and lung were detected after administration of the highest dose of extract for 28 days in sub-acute assay.Hematological analysis showed prominent elevations in total white blood cells in male rats and neutrophils count in female rats after exposure to 500 mg/kg of A.affine extract.In biochemical evaluations,significant increases in serum creatinine level(female rats,250 and 500 mg/kg)and in aspartate aminotransferase(male and female rate,500 mg/kg)and alanine aminotransferase(male,250 and 500 mg/kg and female,500 mg/kg)activities,however,notable decreases in serum blood glucose(male rats,125 and 500 mg/kg),triglycerides(male rats,500 mg/kg and female rates,250 mg/kg),and low-density lipoprotein cholesterol levels(male,250 mg/kg)were found.Histological examinations presented slight portal inflammation in liver tissue,moderate pneumocyte hyperplasia,congestion and peri-bronchial inflammation in lung tissue,and mild histiocytosis and lymphoid follicular activation in spleen tissue after exposure to 500 mg/kg of A.affine extract in male and female animals.Conclusions:The present investigation reveals the safety of A.affine extract at doses of lower than 250 mg/kg in rats and monitoring of lung,spleen,and liver functions is suggested during excessive and prolonged uses.     

Protective Effects of Cannabis sativa on chemotherapy-induced nausea in a rat: Involvement of CB1 receptors

Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (eight animals per group): Group 1: Normal control (saline i.p.). Group 2: Rats received cyclophosphamide (200 mg/kg i.p.) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg i.p.) across Days 1–7, and C. sativa (20 and 40 mg/kg s.c.) was administered on cyclophosphamide days 4–7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5-HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestinal homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5-HT, dopamine and noradrenaline, as well as decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa also improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R.     

Medical Cannabis Program Sustainability in the Era of Recreational Cannabis

PurposeSince October 2022, a total of 21 states have enacted both medical-use and adult-use cannabis legalization, each with their own unique set of laws, regulations, implementation, structures, and enforcement (“policies”). Unlike adult-use programs, medical-use programs often represent a safer and affordable option for patients with diverse needs; however, current evidence suggests that medical-use program activity decreases after implementation of adult-use retail. The current study compares medical patient registration data and medical- and adult-use retail data from 3 distinct medical- and adult-use states (Colorado, Massachusetts, and Oregon) in the time after adult-use retail implementation in each state.MethodsTo investigate changes in medical cannabis programs with simultaneous adult-use legalization, correlation and linear regression analyses were used to assess outcome measures: (1) medical-use retail sales; (2) adult-use retail sales; and (3) number of registered medical patients in all fiscal quarters after adult-use retail sales were implemented in each state to September 2022.FindingsAdult-use cannabis sales increased significantly over time in all 3 states. However, both medical-use sales and number of medical patients registered in the states increased only in Massachusetts.ImplicationsResults indicate that states’ preexisting medical-use programs may undergo critical changes after adult-use cannabis legalization is enacted and implemented. Key policy and program differences, such as regulatory differences in the implementation of adult-use retail sales, may have differential impacts on medical-use programs. For continued patient access, it is critical that future research assess the differences within and between states’ medical-use and adult-use programs that permit sustainability of medical-use programs alongside adult-use legalization and implementation.     

La nigelle cultiv’ée : Nigella sativa L. (Ranunculaceae)

The seeds ofNigella sativa L. (Ranunculaceae), commonly known as black seed or black cumin, are widely used in folk medicine for the treatment and prevention of a number of diseases. The seeds contain both fixed and essential oils as well as proteins, alkaloids and saponin. Much of the biological activities of the seeds has been shown to result from thymoquinone, which is the major component of the essential oil and also present in the fixed oil. The pharmacological properties of the seeds’ crude extracts and some of their active constituents-for example, volatile oil and thymoquinone-include anti-oxidant, anti-inflammatory, analgesic, antimutagenic, antineoplastic, antihepatotoxic, antinephrotoxic, respiratory and immunological, hypoglycaemic, antiulcer, antimicrobial and antiparasitic activity. The seeds are characterized by very low toxicity. A large number of studies support the potential use ofN. sativa in therapeutics.     

Purification and properties of a beta-lactamase from Alcaligenes dentrificans subsp. xylosoxydans

A penicillin beta-lactamase was purified from a strain of Alcaligenes dentrificans subsp. xylosoxydans resistant to beta-lactam antibiotics. The purified enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis, and its molecular weight was 18,000 from sodium dodecylsulphate-acrylamide gel electrophoresis and gel filtration. Its isoelectric point was 9.8, the optimal pH was 8.5 and the optimal temperature was 35 degrees C. The enzyme hydrolyzed penicillin G and ampicillin more rapidly than cephalosporins. Relative rates, with penicillin G as 100, were: ampicillin, 102; carbenicillin, 15; cloxacillin, less than 1; piperacillin, 9; cephaloridine, 41; cefoperazone, 36; cefpiramide, 36 and cefmenoxime, 14. Clavulanic acid, sulbactam, imipenem, and cephamycins had low affinities for the enzyme. The enzyme activity was inhibited by iodine, Hg2+, clavulanic acid and sulbactam.     

The accuracy of aerial triangulation products automatically generated from hyper-spatial resolution digital aerial photography

In recent years, unmanned airborne systems (UAS) have emerged as an important platform for collecting hyper-spatial resolution airborne remote sensing data. Using this hyper-spatial resolution imagery as input, modern aerial triangulation (AT) techniques, also known as structure-from-motion or SfM, can rapidly produce orthophotos and digital surface models (DSMs) at fine scales. Such data hold great promise for a number of applications, including routine and post-disaster assessment of transportation infrastructure, which provided the impetus for this research. Using hyper-spatial resolution (0.002 m) natural colour digital aerial photography acquired from a low-altitude UAS as input images, this research systematically investigated the horizontal and vertical accuracy of the AT generated orthophotos and DSMs, respectively. Hyper-spatial resolution aerial data were collected for a total of 28 study sites and, for each study site, coordinate information of 16 ground control points (GCPs) was collected using a survey grade real-time kinematic (RTK) Global Navigation Satellite System. Among the 16 GCPs for each site, 10 were used to calibrate the AT process while the remaining six GCPs were reserved to evaluate the horizontal and vertical accuracy of the orthophotos and DSMs. An average horizontal root mean squared error (RMSE) of 0.004 m and a vertical RMSE of 0.007 m across all sites indicate great promise for AT processed hyper-spatial resolution airborne remote sensing data to play a significant role in transportation infrastructure monitoring, particularly when considering the horizontal and vertical accuracy of the surveyed GCPs (0.004 and 0.006 m, respectively).     

In vitro anti-inflammatory,in silico molecular docking and molecular dynamics simulation of oleanane-type triterpenes from aerial parts of Mussaenda recurvata

Bioactive-guided investigation of the aerial parts of Mussaenda recurvata Naiki, Tagane, and Yahara (Rubiaceae) led to the isolation of four triterpenes, including two new triterpenes recurvatanes A and B (1 and 2), along with two known compounds 3β,6β,23-trihydroxyolean-12-en-28-oic acid (3) and 3β,6β,19α,23-tetrahydroxyolean-12-en-28-oic acid (4). The chemical structures of the compounds were identified from spectroscopic data and by comparison with the literature. A comprehensive review of NMR data of the oleanane-type triterpenes bearing 3-hydroxy and 4-hydroxymethylene groups indicated the characteristic spectroscopic features in this series. Compounds 1–4 were evaluated for the inhibitory NO production in LPS-stimulated RAW264.7 cells. Compounds 2 and 3 showed a moderate reduction of nitrite accumulation with IC₅₀ values of 55.63 ± 2.52 and 60.08 ± 3.17 μM, respectively. Molecular docking model dedicated to compound 3 or pose 420, which is the best candidate among docking poses of compounds 1–4 interacted well with the crystal structure of enzyme 4WCU: PDB. The best ligand molecule, pose 420 in terms of binding energy obtained from docking studies on molecular dynamics (MD) simulations for 100 ns exhibited non-bonding interactions with the protein and remained stable inside the active site.

Two new triterpenes recurvatanes A and B were isolated from Mussaenda recurvata using bioactive-guided investigation.     

Neuroprotective gene profile in the brain of magnesium-deficient mice.

BACKGROUND: Magnesium (Mg) deficiency may lead to serious metabolic, biological and organic dysfunctions, and cause various clinical disorders. In the current study, we explore endothelial cell activation, inflammation and cell death induced in the brain of adult mice by Mg-deficient diet. METHODS AND RESULTS: Neither TNFalpha, substance P, sTNFRI, sTNFRII proteins (ELISA), nor TNFalpha, adherence molecules and prolactin mRNAs, nor NK1R (immunohistochemistry on brain sections) were up-regulated. No inflammatory infiltrates and no apoptotic cells were observed. Using cDNA assay, we showed a neuroprotective, anti-apoptotic and neurotrophic gene expression profile in the brain at early stage of hypomagnesemia. As a model for neuronal injury, mild sound stimulation of Mg-deficient mice without convulsive seizures triggers neither the release of substance P, nor the development of an inflammatory process or cell death in the brain. CONCLUSION: Our results suggest that Mg-deficiency in mice favours the development of a neuroprotective environment in the brain.     

Partial regeneration/proliferation of the beta-cells in the islets of Langerhans by Nigella sativa L. in streptozotocin-induced diabetic rats

This experiment was carried out to investigate the effect of N. sativa L. on histopathology of pancreatic beta-cells, and blood insulin and glucose concentrations in streptozotocin-induced diabetic rats. Fifty male Wistar rats (200-250 g) were divided into two experimental groups (diabetics with no treatment and diabetics with N. sativa L. treatment), each containing twenty-five rats. Diabetes was induced in both groups by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg). The experimental animals in both groups became diabetic within 24 hours after the administration of STZ. The rats in N. sativa L.-treated group were given the daily intraperitoneal injection of 0.20 ml/kg of N. sativa L. volatile oil for 30 days starting the day after STZ injection. Control rats received only the same amount of normal saline solution. The rats in both groups received the last injection 24 hours before the sacrification and 5 randomly-selected rats in each group were sacrificed before, and the 1, 10, 20 and 30 days after the STZ injection to collect blood and pancreatic tissue samples. The N. sativa L. treatment caused a decrease in the elevated serum glucose, an increase in the lowered serum insulin concentrations and partial regeneration/ proliferation of pancreatic beta-cells in STZ-induced diabetic rats with the elapse of the experiment. It is concluded that the hypoglycaemic action of N. sativa L. could be partly due to amelioration in the beta-cells of pancreatic islets causing an increase in insulin secretion. More studies are needed to demonstrate the exact mechanism of action of N. sativa L. on ameliorated blood glucose concentration in STZ-induced diabetes.     

Microchemical analysis for 13 constituents of plasma from healthy children.

Normal values for 13 chemical constituents of plasma were estimated from results for 837 presumably healthy children. Ninety microliters of specimen was analyzed for lactate dehydrogenase, aspartate aminotransferase, alkaline phosphatase, inorganic phosphorus, total calcium, total cholesterol, total proteins, albumin, uric acid, urea nitrogen, alanine aminotransferase, total bilirubin, and glucose. We used two Abbott ABA-100 Bichromatic Analyzers interfaced directly to the ABA Data Management System. For each test age- and sex-related variations were assessed and normal values were estimated for six different age groups.     

A beta-lactamase-overproducing strain of Alcaligenes denitrificans subsp. xylosoxydans isolated from a case of meningitis.

A resistant (R) clinical isolate of Alcaligenes denitrificans subsp. xylosoxydans was recovered from CSF during treatment including piperacillin. This variant selected in vivo, and a second variant obtained in vitro from the initially susceptible (S) strain, both exhibited resistance to penicillins (ticarcillin, piperacillin) and cephalosporins, but remained susceptible to latamoxef and imipenem. Clavulanate (2 mg/L) restored the susceptibility of the two R-variants to penicillins. A beta-lactamase of pI 9.5 was detected in both S and R strains, but overproduction was observed only in the in-vivo and in-vitro R-variants. This inducible beta-lactamase hydrolysed benzylpenicillin, cephalothin and cephaloridine efficiently, but amoxycillin, ticarcillin and cefoperazone were only moderate substrates. The enzyme was inhibited by clavulanate, cloxacillin and imipenem (IC50 between 3 and 9 mM), but not by aztreonam and chloride ions (1 mM). Resistance to beta-lactams was not transferable by conjugation to Escherichia coli or Pseudomonas aeruginosa, and DNA agarose gel electrophoresis indicated that no plasmid was present in the isolates. Restriction patterns of chromosomal DNA isolated from the S and R isolates were similar after digestion by NotI and HindIII.     

Chemical constituents from the stems of Machilus philippinensis Merr. and the neuroprotective activity of cinnamophilin

The Machilus genus (Lauraceae) had been extensively utilized in folk medicine due to its broad range of bioactivities. In the present study, a series of chromatographic separations of the methanol extract of stems of M. philippinensis led to the identification of thirty eight compounds totally. Among these, biscinnamophilin (1), machilupins A–C (2–4), machilutone A (5), and machilusoxide A (6) were new compounds reported for the first time. In addition, 5 was characterized with a unprecedented carbon skeleton. Other known compounds, including the major compounds cinnamophilin (7) and meso-dihydroguaiaretic acid (8), are identified by comparison of their physical and spectroscopic data with reported values. One of the reported compounds, cinnamophilin A (10), should be revised as dehydroguaiaretic acid (9) after careful comparison of all the ¹H and ¹³C NMR data. Moreover, the neuroprotective activity of cinnamophilin (7) was examined in a primary cortical neuron culture and the results indicated that 7 was effective against glutamate induced excitotoxicity.

The Machilus genus (Lauraceae) had been extensively utilized in folk medicine due to its broad range of bioactivities.