Curcumenol from Curcuma zedoaria: a second monoclinic modification

The title compound, systematic name 9-isopropyl­idene-2,6-dimethyl-11-oxatricyclo­[6.2.1.01,5]undec-6-en-8-ol, C15H22O2, which crystallizes with two mol­ecules of similar conformation in the asymmetric unit, features three fused rings, two of which are five-membered and the third six-membered. Of the two five-membered rings, the one with an O atom has a distinct envelope shape (with the O atom representing the flap). The six-membered ring is also envelope-shaped as it shares a common O atom with the five-membered ring. In the crystal, the two independent mol­ecules are linked by a pair of O—H⋯O hydrogen bonds, generating a dimer

Essential Oil Content of the Rhizome of Curcuma purpurascens

Curcuma purpurascens Bl., belonging to the Zingiberaceae family, is known as temu tis in Yogyakarta, Indonesia. In this study, the hydrodistilled dried ground rhizome oil was investigated for its chemical content and antiproliferative activity against selected human carcinoma cell lines (MCF7, Ca Ski, A549, HT29, and HCT116) and a normal human lung fibroblast cell line (MRC5). Results from GC-MS and GC-FID analysis of the rhizome oil of temu tis showed turmerone as the major component, followed by germacrone, ar-turmerone, germacrene-B, and curlone. The rhizome oil of temu tis exhibited strong cytotoxicity against HT29 cells (IC50 value of 4.9 ± 0.4 μg/mL), weak cytotoxicity against A549, Ca Ski, and HCT116 cells (with IC50 values of 46.3 ± 0.7, 32.5 ± 1.1, and 35.0 ± 0.3 μg/mL, resp.), and no inhibitory effect against MCF7 cells. It exhibited mild cytotoxicity against a noncancerous human lung fibroblast cell line (MRC5), with an IC50 value of 25.2 ± 2.7 μg/mL. This is the first report on the chemical composition of this rhizome’s oil and its selective antiproliferative effect on HT29. The obtained data provided a basis for further investigation of the mode of cell death

Toxicity of Malaysian Medicinal Plant Extracts Against Sitophilus oryzae and Rhyzopertha dominica

The insecticidal activities of extracts from 22 Malaysian medicinal plant extracts from 8 botanical families were tested against rice weevil: Sitophilus oryzae (L.) and lesser grain borer: Rhyzopertha dominica (F.). The extracts were obtained using hexane, methanol, and dichloromethane to extract potential biopesticides from dried leaves. The toxicity levels were examined periodically based on antifeedant activity and contact toxicity assays using treated grain assay. Hexane extracts of Alpinia conchigera, Alpinia scabra, Curcuma mangga, Curcuma purpurascens, Goniothalamus tapisoides, Piper sarmentosum , and methanol extracts of Curcuma aeruginosa, C. mangga , and Mitragyna speciosa were the most potent extracts against S. oryzae and R. dominica with lethal concentration (LC50) values of ≤ 0.42 mg/mL and ≤ 0.49 mg/mL, respectively. The contact toxicity test results showed that methanol extracts of C. aeruginosa and C. mangga , dichloromethane extracts of Cryptocarya nigra , and hexane extracts of C. mangga, and C. purpurascens resulted in 100% mortality of both pests within 28 days exposure of 5 mg/cm2 concentration

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Chemical constituents from the rhizomes of Curcuma zedoaria and Curcuma purpurascens and assessment of their biological activities / Omer Abdalla Ahmed Hamdi

Curcuma zedoaria (Christm.) Rosc. (local name: Temu putih) and Curcuma purpurascens are two medicinally important plants of the genus Curucma and grow abundantly in Asian countries including Malaysia and Indonesia. These two plants are extensively used in the traditional medicinal practice of Malaysia and many other countries of the world for the treatment of various ailments. Phytochemical investigation of the rhizomes of C. zedoaria and C. purpurascens resulted in the isolation of 27 compounds. C. zedoaria afforded eighteen sesquiterpenes, including eight germacrane type (dehydrocurdione 19, curdione 20, furanodiene 21, furanodienone 22, germacrone 23, germacrone 4,5-epoxide 24, germacrone 1,10-epoxide 25, and zederone 26), four guaiane type (gweicurculactone 41, curcumenol 42, curcumenol second monoclinic 150, isoprocurcumenol 43, and procurcumenol 44), one seco-guaiane (curcuzedoalide 62), one elemane (curzerenone 111), one humulane (zerumbone epoxide 151), one cadianene (comosone II 104), one carabrane (curcumenone 65), and one spirolactone type (curcumanolide 101). The work also resulted in the isolation of three labdane diterpenes (labda-8(17), 12 diene-15, 16 dial 127, calcaractrin A 128, and zerumin A 129, which are reported for the first time from C. zedoaria. Phytochemical investigation of C. purpurascens produced five compounds including one bisabolane (ar-turmernone 74) and one guaiane (zedoalactone B 60) sesquiterpene while the rest three are curcuminoids curcumin 138, bisdemethoxycurcumin 139, demethoxycurcumin 140). A total of 34 compounds were identified through the GC and GC-MS spectroscopic analysis of the essential oil obtained by hydrodistillation of C. putpurascens. The major compounds were ar-turmerone 74 (9.4%), germacrone 23 (13.2%), and turmerone 80 (13.5 %). Supercritical fluid extraction of C. purpurascens rhizomes showed that the optimum parameters for higher yield and selective extraction could be obtained at the temperature of 313 K, with ii the pressure 10.34 MPa and the flow rate of liquid CO2 at 12 ml/min. Open column chromatography on silica gel (CC), thin layer chromatography (TLC), preparative thin layer chromatography (PTLC), high performance liquid chromatography (HPLC), and size exclusion chromatography by Sephadex® (LH-20) were used for the detection and isolation of the compounds. Extensive spectroscopic and chromatographic analysis including 1D and 2D NMR (1H NMR, 13C NMR, DEPT, COSY, HMBC, HSQC, and NOESY), IR, UV, GC-MS, LC-MS were used for the structure elucidation of the isolated compounds. X-ray crystallographic analysis was performed on the second monoclinic crystals of curcumenol (151) which is new dimer crystals isolated from C. zedoaria. Isolated compounds were subjected to cytotoxicity, anti-oxidant and neuroprotective assays. Curcumenol (42) and dehydrocurdione (19) showed the highest protection (100%) against hydrogen peroxide induced oxidative stress in NG108-15 cells at the concentrations of 4 and 8 μM, respectively. In the oxygen radical antioxidant capacity assay, zerumbone epoxide (151) showed the highest level of antioxidant activity with a Trolox equivalent (TE) of 35.41 μM per 100 μg of sample. In the MTT based cytotoxicity assay against four cancer cell lines (CaSki, MCF-7, PC-3 and HT-29) curcumenol (42) and curcumenone (65) displayed strong antiproliferative activity (IC50 9.3 and 8.3 μg/ml, respectively). A quantum chemical study was performed to investigate its relationship with cytotoxic activity and revealed that the dipole moment (μ), molecular volume (V), molecular area (A), polarizability (α) and hydrophobicity (log P) are the most important descriptors that influence the cytotoxic activity of the compounds under investigation. The essential oil obtained the hydrodistillation exhibited strong cytotoxicity against HT29 cells but mild cytotoxicity against the non-cancerous human lung fibroblast cell line (MRC5). The two most active compounds; curcumenol (42) and curcumenone (65), were investigated for their binding to human serum albumin (HSA), a transportation protein of human blood. The spectroflurometric analysis, in conjunction with molecular docking study suggested that both curcumenol (42) and curcumenone (65) could bind to binding sites I and II of HSA with intermediate affinity while site I was the preferred binding site for both molecules

A Preliminary Qualitative Study of Two Common Acacia Species in Sudan

This research is dealing with the analysis of tannins of two common Acacia species of Sudan i.e. Acacia nilotica and Acacia seyal. Bark samples from collections of the two acacia species were extracted with distilled water, 80% methanol and 70% acetone. Two sets of extraction were made, one by boiling, and the other by shaking the samples in the respective solvent for eight hours at room temperature. It was found that the 70% acetone was a more efficient solvent than either water or 80% methanol. In addition, qualitative analysis of the phytochemicals showed that the fruits (garad) contain tannins materials, flavonoids and coumarins

Spectrofluorometric and Molecular Docking Studies on the Binding of Curcumenol and Curcumenone to Human Serum Albumin

Curcumenol and curcumenone are two major constituents of the plants of medicinally important genus of Curcuma, and often govern the pharmacological effect of these plant extracts. These two compounds, isolated from C. zedoaria rhizomes were studied for their binding to human serum albumin (HSA) using the fluorescence quench titration method. Molecular docking was also performed to get a more detailed insight into their interaction with HSA at the binding site. Additions of these sesquiterpenes to HSA produced significant fluorescence quenching and blue shifts in the emission spectra of HSA. Analysis of the fluorescence data pointed toward moderate binding affinity between the ligands and HSA, with curcumenone showing a relatively higher binding constant (2.46 × 105 M−1) in comparison to curcumenol (1.97 × 104 M−1). Cluster analyses revealed that site I is the preferred binding site for both molecules with a minimum binding energy of −6.77 kcal·mol−1. However, binding of these two molecules to site II cannot be ruled out as the binding energies were found to be −5.72 and −5.74 kcal·mol−1 for curcumenol and curcumenone, respectively. The interactions of both ligands with HSA involved hydrophobic interactions as well as hydrogen bonding

Bio-guided isolation and bioinformatic studies of cytotoxic phytosterols from Acanthospermum hispidum DC against breast (MCF7) and colorectal (HT29) cancer cells

Acanthospermum hispidum DC (Asteraceae), a traditional medicinal plant, plays a role as an alternative remedy for various diseases, such as bacterial and viral infections, jaundice, malaria, fever, gastrointestinal disorders, headache, convulsions, and snake bites. Flavonoids, alkaloids, saponins, tannins, terpenes, steroids, and cardioactive glycosides are the distinct classes of metabolites in the plant. Although A. hispidum was suggested as a promising antitumor phytomedicine, no studies identified its potential cytotoxic components. In this study, the cytotoxic compounds of A. hispidum were isolated using chromatographic techniques guided by in vitro MTT cytotoxicity assay against selected cancer cell lines; breast cancer (MCF7), colorectal adenocarcinoma (HT29), and hepatoblastoma (HepG2). The selective index (SI) was assessed on MRC5 (Normal human fetal lung fibroblast) cell line. The dichloromethane fraction (DCM) showed remarkable cytotoxic activity against MCF7 and HT29 (%Cell viability; 46.15 and 60.5, respectively). Hence, the main bioactive fraction from DCM was purified to afford two phytosterols; stigmasterol (1) and β-sitosterol (2), which were identified by 1-D and 2-D NMR spectroscopy. Cytotoxic evaluation of 1 and 2 revealed that β-sitosterol showed better selective cytotoxicity against MCF7 and HT29 (IC50 4.07 μg/mL, SI 2.63; IC50 4.52 μg/mL, SI 2.37) compared to stigmasterol (IC50 5.43 μg/mL, SI 1.38; IC50 4.21 μg/mL, SI 1.78), respectively. Bioinformatic assessments of drug-likeness and ADMET properties demonstrated that most criteria were obeyed by the investigated compounds except for their poor solubility, which recommended the preparation of special dosage forms, such as nanoformulation to enhance their oral bioavailability. Swiss Target prediction indicated that nuclear receptors represent the main target class (40%). Whereas caspase-3 stimulant activity (a key enzyme in apoptosis) was predicted by the PASS prediction tool as a potential anticancer mechanism. Our study suggests A. hispidum as a potential source of bioactive phytosterols and as a chemopreventive medicinal plant