Isoquinoline alkaloids isolated from Glaucium corniculatum var. corniculatum and Glaucium grandiflorum subsp. refractum var. torquatum with bioactivity studies.

CONTEXT: The genus Glaucium Mill., one of the important Papaveraceae family plants, is rich in isoquinoline alkaloids and distributed worldwide. OBJECTIVE: Isolation and identification of bioactive alkaloids from Glaucium grandiflorum Boiss. & Huet. subsp. refractum (Nabelek) Mory var. torquatum (Cullen) Mory and G. corniculatum (L.) Rudolph var. corniculatum (Aslan 2012), and investigation of their antioxidant and anticholinesterase activities. MATERIALS AND METHODS: The aerial parts of each plant were dried, powdered, and percolated with methanol, then each extract was fractionated between 50% aqueous acetic acid and petroleum. Their aqueous acidic layer was adjusted to pH 7-8 with NH4OH and extracted with chloroform, the extract was subjected to CC separation and isolation. Structures of the isolated alkaloids were elucidated by 1D and 2D-NMR and mass spectral analyses. The alkaloid extracts and their pure alkaloids were tested for anti-cholinesterase (AChE and BuChE) and antioxidant (ABTS, CUPRAC, ß-carotene linoleic acid tests) activities in vitro. RESULTS: Methanol extracts of Glaucium grandiflorum subsp. refractum var. torquatum and G. corniculatum var. corniculatum afforded a novel compound glauciumoline and seven known isoquinoline alkaloids three of which have an aporphine-type and the other five have a protopine-type skeleton. Among them, trans-protopinium (7) and cis-protopinium (8) were isolated from a Glaucium species for the first time. Tertiary amine extracts (TAEs) of both plants showed very strong acetylcholinesterase inhibitory activity. The TAE of the plants also showed strong antioxidant activity while the isolated alkaloids showed no meaningful activity in the anticholinesterase and antioxidant tests. DISCUSSION AND CONCLUSIONS: Glaucium species are considered promising therapeutic agents in the treatment of Alzheimer's disease.

Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii Pesmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin.

Ancient physicians frequently used the resin of Ferula species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of Ferula species. The dichloromethane extract of the roots of Ferula huber-morathii exhibited cytotoxic activities against COLO 205 (colon), K-562 (lymphoblast), and MCF-7 (breast) cancer cell lines (IC50 = 52 µg/mL, 72 µg/mL, and 20 µg/mL, respectively). Fifteen sesquiterpene coumarin ethers with cytotoxic activity were isolated from the dichloromethane extract of the roots of F. huber-morathii using bioactivity-directed isolation studies. Extensive spectroscopic analyses and chemical transformations have elucidated the structures of these sesquiterpene coumarin ethers as conferone (1), conferol (2), feselol (3), badrakemone (4), mogoltadone (5), farnesiferol A (6), farnesiferol A acetate (7), gummosin (8), ferukrin (9), ferukrin acetate (10), deacetylkellerin (11), kellerin (12), samarcandone (13), samarcandin (14), and samarcandin acetate (15). The absolute configuration of samarcandin (14) was unequivocally determined by the X-ray crystallographic analysis of the semi-synthetic (R)-MTPA ester of samarcandin (24). Conferol (2) and mogoltadone (5) were found to be the most potent cytotoxic compounds against all three cancer cell lines; furthermore, these compounds exhibit low cytotoxic activity against the non-cancerous human umbilical vein epithelial cells (HUVEC) cell line. Investigation of the biological activity mechanisms of mogoltadone (5) revealed that while suppressing the levels of Bcl-XL and procaspase-3 in the COLO 205 cancer cell line, it did not have a significant effect on the Bcl-XL, caspase-3, and ß-catenin protein levels of the HUVEC cell line, which may explain the cytotoxic selectivity of mogoltadone (5) on cancer cell lines.

Text presentation or video: Malaysian university students' preferences with synchronous and asynchronous learning.

In overcoming the obstacles of online learning with the current Covid-19 pandemic crisis, synchronous and asynchronous learning has been a significant part of teaching strategies applied by educators to construct a collaborative online environment with Malaysian university students. Synchronous learning has always been the most effective strategy for social learning, while asynchronous learning allows students to learn on their own schedule. Moreover, despite having many educational platforms created for higher educational settings, the practicality of selection between two teaching-learning approaches of text-presentation and video is still a debate among teachers/ lecturers with students' learning styles. Therefore, this paper explored Malaysian university students' preferences between synchronous and asynchronous learning modes with text-presentation or video. Qualitative and quantitative data from 178 participants from both public and private universities were collected via open and close-ended questions in the designed questionnaire. The findings indicated that 68% of the students preferred synchronous learning mode compared to asynchronous. Meanwhile, 39% of the students favoured both text-presentation and video learning tools to be implemented in synchronous and asynchronous approaches as it provided them better opportunities to grasp the learning content better. Thus, it can be concluded that the synchronous learning mode is preferred if only one method is provided as the students highly value the teacher's presence for ease of communication, but students prefer a range of delivery methods. Moreover, the students also displayed a strong preference for applying both text-presentation and video to achieve their learning outcomes. Thus, it is suggested that the university lecturers need to explore and apply interactive pedagogical methods in online teaching-learning process, while contributing to the development of motivation, participation, and engagement among the university students in acquiring their subjects. As such, the findings of this study have informed the pedagogical implications, and further studies are mandatory.

Phytochemical analysis and molecular docking studies of two endemic varieties of Salvia sericeotomentosa.

The use of medicinal plants for treating various diseases dates back thousands of years and has been a part of many cultures around the world. Various parts of plants, including roots, leaves, and flowers, and their extracts have been used to develop remedies to cure different ailments like fever, pain, inflammation, infections, among others. In this research, the aerial parts of both Salvia varieties were extracted with ethanol and water to obtain infusion and decoction, separately. S. sericeotomentosa var. hatayica Celep & Dogan (SH) and Salvia sericeotomentosa Rech. f. var. sericeotomentosa (ST) plants were chemically analyzed for polar compounds using LC-HRMS for the first time. All SH and ST extracts were found to be very rich in rosmarinic acid, salvianolic acid B, hispidulin-7-O-glucoside, and caffeic acid. The study also investigated the antiinflammatory and carbonic anhydrase inhibition properties of the most abundant secondary metabolites extracted from SH and ST. In silico studies were conducted for the first time to explore the effects of these metabolites on TNF-α, iNOS, and human carbonic anhydrase isoenzymes (hCAI and hCAII). Salvianolic acid B should be considered a strong antiinflammatory agent and a carbonic anhydrase I and II inhibitors due to low binding energy scores with the tested enzymes (TNF-α: -12.391 kcal/mol), (iNOS: -7.547 kcal/mol), (hCAI: -7.877 kcal/mol), and (hCAII: -4.312 kcal/mol).

Intravaginal treatment with Marantodes pumilum (Kacip Fatimah) ameliorates vaginal atrophy in rats with post-menopausal condition.

ETHNOPHARMACOLOGICAL RELEVANCE: Marantodes pumilum (MP) (Kacip Fatimah) is used to maintain the well-being of post-menopausal women. However, its role in ameliorating post menopause-related vaginal atrophy (VA) is unknown. AIMS: To investigate the ability of intravaginal MP gel treatment to ameliorate VA in sex-steroid deficient condition, mimicking post-menopause. METHODS: Ovariectomized female Sprague-Dawley rats received MP (100 µg/ml, 250 µg/ml and 500 µg/ml) and estriol (E) gels intravaginally for seven consecutive days. Rats were then euthanized and vagina was harvested and subjected for histological and protein expression and distribution analyses. Vaginal ultrastructure was observed by transmission electron microscopy (TEM). RESULTS: Thickness of vaginal epithelium increased with increasing intravaginal MP doses. Additionally, increased in expression and distribution of proliferative protein i.e. PCNA, tight junction protein i.e. occludin, water channel proteins i.e. AQP-1 and AQP-2 and proton extruder protein i.e. V-ATPase A1 were observed in the vagina following intravaginal MP and E gels treatment. Intravaginal MP and E gels also induced desmosome formation and approximation of the intercellular spaces between the vaginal epithelium. CONCLUSIONS: Intravaginal MP was able to ameliorate features associated with VA; thus, it has potential to be used as an agent to treat this condition.

Antibacterial Activities of Pyrenylated Coumarins from the Roots of Prangos hulusii.

The dichloromethane extract of the roots of Prangos hulusii, a recently described endemic species from Turkey, has yielded nine known and one new prenylated coumarins. The structures were elucidated by spectroscopic methods and direct comparison with the reference compounds where available. The root extract and its prenylated coumarins exhibit antimicrobial activity against nine standard and six clinically isolated strains at a concentration between 5 and 125 µg/mL. In particular, the new coumarin, 4'-senecioiloxyosthol (1), displayed 5 µg/mL MIC (Minimum Inhibitory Concentration) value against Bacillus subtilis ATCC 9372, murraol (4) and auraptenol (5) showed 63 µg/mL MIC value against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 9372, and isoimperatorin (9) exhibited 16 µg/mL MIC value.

Herbal haemorrhoidal cream for haemorrhoids.

Although hemorrhoids are one of the most common diseases in the world, the exact etiology underlying the development of hemorrhoids is not clear. Many different ointments are currently used to treat hemorrhoids; however, there is little evidence of the efficacy of these treatments to support their use. The aim of this study was to compare different herbal creams used for the treatment of hemorrhoids. Twenty-eight male Wistar albino rats, 6-8 weeks old and weighing 160-180 g, were used in this study as 1-control, 2-croton oil, 3-croton oil+fig leaves+artichoke leaves+walnut husks and 4-croton oil+fig leaves+artichoke leaves+walnut husks+horse chestnut fruit. After 3 days of croton oil application, rats were treated with 0.1 ml of cream or saline twice a day for 15 days by syringe. Tissue and blood samples were collected for histological, immunohistochemical and biochemical studies. Statistical significance was determined using one-way ANOVA followed by Tukey's multiple comparison tests. Croton oil administration resulted in severe inflammation. The third group showed partial improvement in inflammation; however, the greatest degree of improvement was seen in the fourth group, and some recovered areas were observed. Myeloperoxidase immunoreactivity was found to be decreased in the third and fourth groups compared to the second group. Additionally, biochemical analyses (Myeloperoxidase, Malondyaldehyde, nitrate/nitrite and nitrotyrosine levels and Superoxide Dismutase activity) were in agreement with the histological and immunohistochemical results. In conclusion, croton oil causes inflammation in the anal area and results in hemorrhoids. Treatment with our herbal hemorrhoid creams demonstrated anti-inflammatory and anti-oxidant effects in this model.

Sequential antibiotic and growth factor releasing chitosan-PAAm semi-IPN hydrogel as a novel wound dressing.

The aim of this study is to prepare a novel wound dressing material which provides burst release of an antibiotic in combination with sustained release of growth factor delivery. This might be beneficial for the prevention of infections and to stimulate wound healing. As a wound dressing material, the semi-interpenetrating network (semi-IPN) hydrogel based on polyacrylamide (PAAm) and chitosan (CS) was synthesized via free radical polymerization. Ethylene glycol dimethacrylate was used for cross-linking of PAAm to form semi-IPN hydrogel. The hydrogel shows high water content (∼1800%, in dry basis) and stable swelling characteristics in the pH range of the wound media (∼4.0-7.4). The antibiotic, piperacillin-tazobactam, which belongs to the penicillin group was loaded into the hydrogel. The therapeutic serum dose of piperacillin-tazobactam for topic introduction was reached at 1st hour of the release. Additionally, in order to increase the mitogenic activity of hydrogel, epidermal growth factor (EGF) was embedded into the CS-PAAm in different amounts. Cell culture studies were performed with L929 mouse fibroblasts and the simulated cell growth was investigated by 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide assay. The successful sustained release behavior of CS-PAAm hydrogel for EGF maintained the presence of EGF in the culture up to 5 days and the highest mitochondrial activities were recorded for the 0.4 µg EGF-loaded/mg of hydrogel group. In conclusion, CS-PAAm semi-IPN hydrogel loaded with piperacillin-tazobactam and EGF could be proposed for an effective system in wound-healing management.

Abietane diterpenoids and triterpenoic acids from Salvia cilicica and their antileishmanial activities.

Bioguided-fractionation of an acetone extract of the roots of Salvia cilicica (Lamiaceae) led to isolation of two new diterpenes, 7-hydroxy-12-methoxy-20-nor-abieta-1,5(10),7,9,12-pentaen-6,14-dione and abieta-8,12-dien-11,14-dione (12-deoxy-royleanone), together with oleanolic acid, ursolic acid, ferruginol, inuroyoleanol and cryptanol. Their structures were determined spectroscopically, which included HREIMS and 2D NMR spectroscopic analysis. The new abietane derivatives showed appreciable in vitro antileishmanial activity against intracellular amastigote forms of both Leishmania donovani (IC(50) values of 170 and 120 nM, respectively) and Leishmania major (IC(50) values of 290 and 180 nM, respectively). The triterpenoic acids were found to be potently active against amastigote (IC(50) values of 7-120 nM) and moderately active against promastigote stages (IC(50) values of 51-137 nM) of the two Leishmania species.