Gypsogenin Battling for a Front Position in the Pentacyclic Triterpenes Game of Thrones on Anti-Cancer Therapy: A Critical Review-Dedicated to the Memory of Professor Hanaa M. Rady.

In the last decade, gypsogenin has attracted widespread attention from medicinal chemists by virtue of its prominent anti-cancer potential. Despite its late identification, gypsogenin has proved itself as a new anti-proliferative player battling for a frontline position among other classic pentacyclic triterpenes such as oleanolic acid, glycyrrhetinic acid, ursolic acid, betulinic acid, and celastrol. Herein, we present the most important reactions of gypsogenin via modification of its four functional groups. Furthermore, we demonstrate insights into the anti-cancer activity of gypsogenin and its semisynthetic derivatives and go further by introducing our perspective to judiciously guide the prospective rational design. The present article opens a new venue for a better exploitation of gypsogenin chemical entity as a lead compound in cancer chemotherapy. To the best of our knowledge, this is the first review article exploring the anti-cancer activity of gypsogenin derivatives.

Investigating the Potential Anti-SARS-CoV-2 and Anti-MERS-CoV Activities of Yellow Necklacepod among Three Selected Medicinal Plants: Extraction, Isolation, Identification, In Vitro, Modes of Action, and Molecular Docking Studies.

The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. The highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode of action for both S. tomentosa and A. judaica showed 99.5% and 92% inhibition, respectively, with virucidal as the main mode of action. Furthermore, the anti-MERS-CoV and anti-SARS-CoV-2 activities of S. tomentosa were measured. Notably, the anti-SARS-CoV-2 activity of S. tomentosa was very high (100%) and anti-MERS-CoV inhibition was slightly lower (96%). Therefore, the phytochemical investigation of the very promising S. tomentosa L. led to the isolation and structural identification of nine compounds (1−9). Then, both the CC50 and IC50 values for the isolated compounds against SARS-CoV-2 were measured. Compound 4 (genistein 4'-methyl ether) achieved superior anti-SARS-CoV-2 activity with an IC50 value of 2.13 µm. Interestingly, the mode of action of S. tomentosa against SARS-CoV-2 showed that both virucidal and adsorption mechanisms were very effective. Additionally, the IC50 values of S. tomentosa against SARS-CoV-2 and MERS-CoV were found to be 1.01 and 3.11 µg/mL, respectively. In addition, all the isolated compounds were subjected to two separate molecular docking studies against the spike (S) and main protease (Mpr°) receptors of SARS-CoV-2.

Protective role of Codiaeum variegatum against genotoxicity induced by carmustine in somatic and germ cells of male mice.

BACKGROUND: Carmustine (Cr) is an important chemotherapeutic drug, widely used in the treatment of brain tumors. Herein, the protective role of Codiaeum variegatum leaves ethyl acetate fraction was determined against genotoxicity of Cr. The technique HPLC-qTOF-MS/MS was used to identify the constituents in C. variegatum. MATERIALS: 90 male mice were used to evaluate micronuclei (MPCEs) in bone marrow, chromosomal aberration (CAs) in bone marrow and mouse spermatocytes, sperm abnormalities, and gene expression (qRT-PCR). The following groups were included, I: Negative control (ethanol 30%), II: Positive control (i.p injected once with 30 mg/kg Cr), III: Control orally treated with C. variegatum at 500 mg/kg, four days. IV-VI: treated with 100, 300, and 500 mg/kg of the plant (4 days) plus a single dose of Cr. RESULTS: In bone marrow, Cr induced significant increase in MPCEs and CAs by 3 and 7-folds respectively over the control. Cr also induced a significant percentage of CAs in spermatocytes in meiosis in the form of univalent (X-Y and autosomal univalent) and also a significant percentage of morphological sperm abnormalities was recorded. A large number of coiled tail abnormalities were detected indicating the effect of Cr in sperm motility. Cr induced an overexpression of p53 gene. C. variegatum mitigated all deleterious genotoxic effects of Cr. Chemical analysis showed that flavones (35.21%) and phenolic acids (17.62%) constitute the main components. CONCLUSIONS: The results indicated that Cr is genotoxic in both somatic and germ cells. The active components in C. variegatum together participate in the obtained protective role.

Hemimycale Arabica Induced Non-Cytotoxic Anti-Migratory Activity in Hepatocellular Carcinoma In Vitro.

OBJECTIVE: In this work, we represented new non-cytotoxic treatments to avoid serious side effects of current used cytotoxic anticancer drugs. These treatments can compensate in finding convenient treatment for each individual case using a single agent from marine sponge Hemimycale arabica. METHODS: The ethanol extract was partitioned by cold sequential liquid-liquid extraction to afford petroleum ether, diethyl ether, dichloromethane and ethyl acetate fractions. Chemical composition of H. arabica was performed by gas-liquid chromatography and gas chromatography-mass spectroscopy. Anticancer activity was evaluated by means of cytotoxicity, apoptosis induction, tumor cell migration inhibition and expression analysis of proliferation and migration-related genes. RESULTS: Our results revealed that all treatments were non-cytotoxic except for dichloromethane fraction which exhibited moderate cytotoxic activity. Caspase-independent apoptosis was induced by total ethanol and dichloromethane fractions while ethyl acetate fraction induces caspase-dependent apoptosis. All treatments inhibited matrix metalloproteinase-independent migration. Petroleum ether and dichloromethane inhibited migration through the down-regulation of FGF and it could be used as anticancer therapy for VEGF-resistance patients. While ethanol inhibited tumor cell migration through down-regulation of all tested genes expression. Ether and ethyl acetate fractions exerted anti-migratory activity without affecting the tested genes. All resuls were statistically significant at p˂0.05. CONCLUSION: Total ethanol extract is a promising non-cytotoxic anticancer agent because of its powerful apoptosis induction and capability to block tumor cell migration. Petroleum ether and ether fractions area weak non-cytotoxic anti-migratory agents. Dichloromethane could be a moderate cytotoxic anti-migratory agent induced caspase-independent apoptosis. It could be used in anticancer therapy for VEGF-resistance patients through downregulation of FGF. Ethyl acetate fraction considered a non-cytotoxic agent exerting moderate anti-migratory activity. The new sponge-derived treatments can solve different resistance problems to find a convenient treatment for each individual case using a single agent.

Alloimperatorin from Ammi majus fruits mitigates Piroxicam-provoked gastric ulcer and hepatorenal toxicity in rats via suppressing oxidative stress and apoptosis.

INTRODUCTION: Fruits of Ammi majus, commonly called bishop's weed, contain a significant amount of furanocoumarins. Alloimperatorin (Allo, 6) was isolated from the free coumarin fraction of fruits, beside 8-hydroxypsoralen (1), methoxsalen (2), heraclin (3), isoimperatorin (4), imperatorin (5), isoheraclenin (7) and heraclenin hydrate (8). Piroxicam (Px) is a widely used pain-relieving drug that demonstrated side effects, including gastric ulceration and hepatorenal toxicity. OBJECTIVE: This study aimed to investigate the protective potential of Alloimperatorin against Px-induced gastric ulceration and hepatorenal toxicity. MATERIAL & METHODS: Rats were divided into four groups: Negative control, Px-induced rats, Allo + Px co-treated group, and Pc + Px co-treated group. Allo (25 mg/kg body weight) and Pc (25 mg/kg body weight) treatments were received 5 days before and 4 days after Px intoxication for 4 days (50 mg/kg body weight). Serum prostaglandin E2 (PG-E2) and liver and kidney functions were measured. Oxidative stress markers were evaluated in the three tissues. Histopathological features and caspase-3 immunoexpression were monitored. RESULTS & DISCUSSION: Px triggered gastric ulceration, increased indices of liver and kidney functions, decreased PG-E2 levels, provoked oxidative stress, and activated caspase-3 immunoexpression. Co-treatment with Allo demonstrated protective activities. CONCLUSION: Alloimperatorin exhibited anti-oxidative, anti-inflammatory, and anti-apoptotic activities.

Pulicaria crispa mitigates nephrotoxicity induced by carbon tetrachloride in rats via regulation oxidative, inflammatory, tubular and glomerular indices.

CONTEXT: Carbon tetrachloride (CCl4) induces oxidative stress in various tissues by altering antioxidants defense system. Recently, there has been a substantial use of phytotherapy to treat different diseases. OBJECTIVE: This study was designed to evaluate the curative effect of Pulicaria crispa (Forssk.) Benth et Hook (Family Asteraceae) aerial parts ethanol extract against CCl4 induced toxicity in rats kidneys. MATERIALS AND METHODS: Nephrotoxicity was induced by intraperitoneal injection with CCl4 in a dose of 0.5 mL/kg b.wt./twice a week for six consecutive weeks. Serum kidney function tests, oxidative stress markers, inflammatory cytokines, nephrotoxicity biomarkers and histopathological observation were evaluated. RESULTS: CCl4 increased serum kidney function parameters, malondialdehyde level, inflammatory cytokines, and nephrotoxicity markers, while decreased certain oxidative stress indices as superoxide dismutase and glutathione refereeing to the control group (p < 0.0001). Administration of P. crispa ethanol extract to CCl4 injured rats attenuated these changes with variable degrees. The results were confirmed through the observed amelioration of the renal histological architectures. CONCLUSION: P. crispa ethanol extract possesses potent curative effect against CCl4-induced nephropathy through improvement of kidney function, oxidative stress, inflammatory and nephrotoxicity index and the renal histopathological features. To establish the therapeutic and pharmacological applications of the plant, additional researches are required.

Genus Sophora: a comprehensive review on secondary chemical metabolites and their biological aspects from past achievements to future perspectives.

Sophora is deemed as one of the most remarkable genera of Fabaceae, and the third largest family of flowering plants. The genus Sophora comprises approximately 52 species, 19 varieties, and 7 forms that are widely distributed in Asia and mildly in Africa. Sophora species are recognized to be substantial sources of broad spectrum biopertinent secondary metabolites namely flavonoids, isoflavonoids, chalcones, chromones, pterocarpans, coumarins, benzofuran derivatives, sterols, saponins (mainly triterpene glycosides), oligostilbenes, and mainly alkaloids. Meanwhile, extracts and isolated compounds from Sophora have been identified to possess several health-promising effects including anti-inflammatory, anti-arthritic, antiplatelets, antipyretic, anticancer, antiviral, antimicrobial, antioxidant, anti-osteoporosis, anti-ulcerative colitis, antidiabetic, anti-obesity, antidiarrheal, and insecticidal activities. Herein, the present review aims to provide comprehensive details about the phytochemicals and biological effects of Sophora species. The review spotlighted on the promising phytonutrients extracted from Sophora and their plethora of bioactivities. The review also clarifies the remaining gaps and thus qualifies and supplies a platform for further investigations of these compounds.

Downregulation of fibrosis and inflammatory signalling pathways in rats liver via Pulicaria crispa aerial parts ethanol extract.

CONTEXT: Liver is a vital organ for the detoxification of toxic substances in the body, where fibrosis is the major cause of liver damage. Pulicaria crispa processes many therapeutic applications such as antioxidant, antimicrobial, anticancer and anti-ulcerative agent. OBJECTIVE: This study aimed to modulate the fibrosis and inflammatory signalling pathways in carbon tetrachloride (CCl4)-induced liver damage in rats via treatment with Pulicaria crispa aerial parts ethanol extract (PCEE). MATERIALS AND METHODS: CCl4 was intraperitoneally injected at a dose of 0.5 mL/kg b.wt./twice a week/six consecutive weeks, PCEE was orally allocated at a dose of 250 mg/kg b.wt./day/six weeks and silymarin was orally administrated at a dose of 100 mg/kg, b.wt/day/six weeks. The plant extract evaluation was done through measuring aspartate and alanine aminotransferases (AST& ALT), alkaline phosphatase (ALP), total lipids (TP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low level glycoprotein-cholesterol (LDL-C), alpha fetoprotein (AFP), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6). The liver architectures were also estimated. RESULT: The phytochemical analysis of the extract showed the presence of sterols and/or triterpenoids. Treatments with plant extract suppressed significantly (p < 0.0001) the levels of AST, ALT, ALP, TP, TG, TC, LDH-C, MDA, NO, AFP, TNF-α and IL-6, while increased (p < 0.0001) the levels of HDL-C, GSH and SOD. The histopathological features confirmed the therapeutic role of the plant extract. CONCLUSION: PCEE succeeded to exert anti-fibrotic, anti-inflammatory and anti- oxidants effects in CCl4-induced liver fibrosis.

Cardenolides and pentacyclic triterpenes isolated from Acokanthera oblongifolia leaves: their biological activities with molecular docking study.

Pentacyclic triterpenes and cardenolides were isolated from Acokanthera oblongifolia leaves. Their chemical structures were determined based on comprehensive 1D and 2D NMR spectroscopy. Their MIC was determined against 12 microorganisms. Their exerted cytotoxicity on the immortalized normal cells, hTERT-RPE1 was assessed by the sulforhodamine-B assay. The viral inhibitory effects of compounds against Newcastle disease virus (NDV) and H5N1 influenza virus IV were evaluated. Four in vitro antioxidant assays were performed in comparison with BHT and trolox and a weak activity was exhibited. Acovenoside A was with potent against H5N1-IV and NDV with IC50 ≤ 3.2 and ≤ 2.1 µg/ml and SI values of 93.75 and 95.23%, respectively, in comparison to ribavirin. Its CC50 record on Vero cells was > 400 and 200 µg/ml, respectively. Acobioside A was the most active compound against a broad range of microbes while Pseudomonas aeruginosa was the most sensitive. Its MIC (0.07 µg/ml) was 1/100-fold of the recorded CC50 (7.1 µg/ml/72 h) against hTERT-RPE1. The molecular docking of compounds on human DNA topoisomerase I (Top1-DNA) and IV glycoprotein hemagglutinin were studied using MOE program. This study has introduced the cardenolides rather than triterpenoids with the best docking score and binding interaction with the active site of the studied proteins.

In vitro chemotherapeutic and antiangiogenic properties of cardenolides from Acokanthera oblongifolia (Hochst.) Codd.

Acovenoside A (Acov-A) and acobioside A (Acob-A) were isolated from Acokanthera oblongifolia. Their anticancer properties were explored regarding, antiproliferative and antiangiogenic activities. The study included screening phase against six cancer cell lines followed by mechanistic investigation against HepG2 cancer cell line. The sulforhodamine-B (SRB) was used to determine their growth inhibitory power. In the other hand, flow cytometry techniques were recorded the cell death type and cell cycle analysis. The clonogenic (colony formation) and wound healing assays, enzyme-linked immunosorbent assay (ELISA) and molecular docking, were performed to evaluate the antiangiogenesis capability. Both compounds were strongly, inhibited four cancer cell lines at GI50 less than 100 nM. The in vitro mechanistic investigation against HepG2 resulted in cell accumulations at G2M phase and induction of apoptosis upon treating cells separately, with 400 nM Acov-A and 200 nM Acob-A. Interestingly, the same concentrations were able to activate caspase-3 by 7.2 and 4.8-fold, respectively. Suppressing the clonogenic capacity of HepG2 cells (20 and 40 nM) and inhibiting the migration of the colon Caco-2 cancer cells were provoke the results of vascular endothelial growth factor receptor2 (VEGFR2) kinase enzyme inactivation. The docked study was highly supportive, to the antiangiogenic approach of both cardenolides. The isolated cardenolides could orchestrate pivotal events in fighting cancer.

Genotoxicity and sperm defects induced by 5-FU in male mice and the possible protective role of Pentas lanceolata-iridoids.

5-Fluorouracil (5-FU) is a widely used antineoplastic drug. In this work, a comprehensive study was performed to detect the extent of chromosomal damage and morphological sperm defects induced by 5-FU in male mice and the possible protective role of the iridoids-rich fraction of Pentas lanceolata leaves (IFPL). Six main groups were examined in micronucleus and chromosomal assays: I- control negative, II- control positive (i.p. treated with single dose of 75 mg/kg 5-FU), III- control plant (orally administrated IFPL, 300 mg/kg, 5 consecutive days), and IV-VI- treated with IFPL (100, 200 and 300 mg/kg, 5 consecutive days) plus 5-FU (i.p. treated at the last day). Samples were taken 24 h post treatment. The study of morphological sperm anomalies, single and repeated treatments were examined and samples were taken after 35 days from the 1st treatment. In bone marrow, 5-FU induced a significant increase in the micro-nucleated polychromatic erythrocytes, chromosome anomalies (CAs) and also cytotoxic effects. A significant percentage of CAs was recorded in spermatocytes after 5-FU treatment reached 22.80 ± 1.32 vs 4.20 ± 0.37 for control (mainly X-Y univalent, 90%). IFPL was recorded to be non-mutagenic in all tests examined. In addition, it alleviated the previous defects in a dose-dependent manner. A significant and dramatic increase in the percentage of morphological sperm defects was recorded after single and repeated treatments with 5-FU reached 13.24 ± 0.24, 30.42 ± 0.32 respectively vs 2.56 ± 0.14 for control. Amorphous head-sperm and sperm with coiled tail were the most pronounced types of abnormalities. Significant protection was detected with the highest tested dose of IFPL. In conclusion: 5-FU demonstrated to be a genotoxic agent. Its genotoxicity in germ cells is serious and may lead to reproductive toxicity, infertility or heritable defects. The results also demonstrated the biosafety of IFPL and its possible protective role in combined treatment with 5-FU.

The ameliorating effect of carotenoid rich fraction extracted from Dunaliella salina microalga against inflammation- associated cardiac dysfunction in obese rats.

The carotenoid rich fraction of microalgae Dunaliella salina (crf-DS) have been receiving great attention, due to they abilities to protect and improve various disorders. The objective of this study is to explore the therapeutic efficiency of crf-DS on obesity-assciated cardiac dysfunction in the high-fat diet (HFD) treated rats. These rats were orally administered with crf-DS (150 mg /kg body weight), for six consecutive weeks in comparison with reference drug(orlistat). Specific cardiac biomarkers were examined including; adiponectin, plasminogen activator inhibitor (PAI-1), glucagon, troponin-I (cTnI). The cell adhesion molecules (VCAM and ICAM), C-reactive protein (CRP), collagen type II (Col II), collagen alpha-1 (III) chain (Col3A1), lipoxygenase activity (LOX), as well as histopathological examination of cardiac tissue were investigated. Results indicated a significant reduction(P ≤ 0.05) in adiponectin and glucagon levels in serum of obese rats. However, cTnI, PAI-1, cell adhesion molecules, CRP, Col II, and Col3A1 and LOX levels declared marked increase. Histopathological examination of cardiac tissue showed fibrosis with severe congestion in the myocardial blood vessels. On the other hand, rats medicated with a crf-DS demonstrated noticeable ameliorating effect in all the measured parameters. Beside, myocardial tissue of obese rats showed no alteration. Hence, It could be concluded that, oral supplementation with crf-DS is able to attenuate cardiac dysfunction in obese rats. Further extended work is needed to exploit, the possible application of D. salina as nutraceuticals and food additives.

Chemical composition and protective role of Pulicaria undulata (L.) C.A. Mey. subsp. undulata against gastric ulcer induced by ethanol in rats.

Pulicaria undulata subsp. undulata (Family; Asteraceae) is a medicinal plant used to treat inflammation. The objective of this study is to explore the protective effect of the ethanol extract of P. undulata subsp. undulata aerial parts against ethanol induced gastric ulcer in rats. The chemical composition of plant extract, the unsaponifiable matter and the fatty acid methyl esters were analyzed. The biological evaluation was carried out through measuring ulcer indices, oxidative stress markers, certain marker enzymes, inflammatory index and the histopathological assessment of the stomach in rats. The total unsaponifiable matter (94.29%) and the fatty acid methyl ester (82.96%) content were identified. Gastric ulcer recorded significant increase in gastric volume and lesion counts (p < 0.0001). Drastic changes in all biochemical parameters under investigation were observed. Protection with plant extract reversed the action of ethanol by variable degrees of improvement in comparison with the reference drug. The presence of carbohydrates and proteins that acted as a mucilage lining the stomach inner wall give its protective action. In conclusion, P. undulata subsp. undulata succeeded to have anti-ulcerative protective effect. The measured biomarkers served as a good mirror to predict gastric ulcer and the presence of carbohydrates, protein and fibers present in the plant extract acted as a mucilage lining the inner intestinal wall and protect against ethanol induced gastric ulcer. Future study will be carried out to identify the biologically active compounds responsible for plant protection against the gastric ulcer.

Pulicaria crispa mitigates gastric ulcer induced by ethanol in rats: role of treatment and auto healing.

Context: Stomach ulcers are the common gastrointestinal disorders worldwide. Objective: This study aimed to investigate the therapeutic impact of Pulicaria crispa aerial parts ethanol extract against gastric ulcer in rats. Materials and methods: Ulcer was induced by one oral dose of ethanol (0.5 ml/100g body weight) on 24 hours empty stomach, then the plant extract (500 mg/kg b.wt.) was orally administered daily for one week. Ranitidine (100 mg/kg b.wt.); as a reference drug was evaluated. Stomach acidity and volume, as well as lesion counts were measured. Levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) were estimated. Assay of different marker enzymes; succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP) and 5'-nucleotidase (5'NT) were determined. Interlukin-10 (IL-10), intracellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor alpha (TNF-α) were also determined. Stomach histopathological assessment was detected. Results: Gastric ulcer showed drastic changes in oxidative stress, cell organelles and inflammatory markers. These biomarkers served as good tools to identify the presence of gastric ulcer. Treatment with P. crispa recorded amelioration in most parameters exceeding the auto healing effect. Conclusion: Healing potency of P. crispa is possibly related to its content of glycosides, coumarins, flavonoids, tannins, sterols and triterpenes.

Antibacterial Activities of Metabolites from Vitis rotundifolia (Muscadine) Roots against Fish Pathogenic Bacteria.

Enteric septicemia of catfish, columnaris disease and streptococcosis, caused by Edwardsiella ictaluri, Flavobacterium columnare and Streptococcus iniae, respectively, are the most common bacterial diseases of economic significance to the pond-raised channel catfish Ictalurus punctatus industry. Certain management practices are used by catfish farmers to prevent large financial losses from these diseases such as the use of commercial antibiotics. In order to discover environmentally benign alternatives, using a rapid bioassay, we evaluated a crude extract from the roots of muscadine Vitis rotundifolia against these fish pathogenic bacteria and determined that the extract was most active against F. columnare. Subsequently, several isolated compounds from the root extract were isolated. Among these isolated compounds, (+)-hopeaphenol (2) and (+)-vitisin A (3) were found to be the most active (bacteriostatic activity only) against F. columnare, with 24-h 50% inhibition concentrations of 4.0 ± 0.7 and 7.7 ± 0.6 mg/L, respectively, and minimum inhibitory concentrations of 9.1 ± 0 mg/L for each compound which were approximately 25X less active than the drug control florfenicol. Efficacy testing of 2 and 3 is necessary to further evaluate the potential for these compounds to be used as antibacterial agents for managing columnaris disease.

Secondary metabolites and biological activity of Pentas species: A minireview.

The genus Pentas belongs to the Rubiaceae family, which contains approximately 40 species. Several Pentas species were reported to be used as a folk treatment by African indigenous people in treating some diseases such as malaria, tapeworms, dysentery, gonorrhea, syphilis and snake poisoning. This article covers the period from 1962 to 2017 and presents an overview of the biological activity of different Pentas species and describes their phytochemical traits. As a conclusion, the main secondary metabolites from Pentas species are quinones, highly oxygenated chromene-based structures, and iridoids. Pentas species are widely used in folk medicine but they have to be more investigated for their medicinal properties.

Marine Inspired 2-(5-Halo-1H-indol-3-yl)-N,N-dimethylethanamines as Modulators of Serotonin Receptors: An Example Illustrating the Power of Bromine as Part of the Uniquely Marine Chemical Space.

In previous studies, we have isolated several marine indole alkaloids and evaluated them in the forced swim test (FST) and locomotor activity test, revealing their potential as antidepressant and sedative drug leads. Amongst the reported metabolites to display such activities was 5-bromo-N,N-dimethyltryptamine. Owing to the importance of the judicious introduction of halogens into drug candidates, we synthesized two series built on a 2-(1H-indol-3-yl)-N,N-dimethylethanamine scaffold with different halogen substitutions. The synthesized compounds were evaluated for their in vitro and in vivo antidepressant and sedative activities using the mouse forced swim and locomotor activity tests. Receptor binding studies of these compounds to serotonin (5-HT) receptors were conducted. Amongst the prepared compounds, 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (1a), 2-(5-bromo-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (1d), 2-(1H-indol-3-yl)-N,N-dimethylethanamine (2a), 2-(5-chloro-1H-indol-3-yl)-N,N-dimethylethanamine (2c), 2-(5-bromo-1H-indol-3-yl)-N,N-dimethylethanamine (2d), and 2-(5-iodo-1H-indol-3-yl)-N,N-dimethylethanamine (2e) have been shown to possess significant antidepressant-like action, while compounds 2c, 2d, and 2e exhibited potent sedative activity. Compounds 2a, 2c, 2d, and 2e showed nanomolar affinities to serotonin receptors 5-HT1A and 5-HT7. The in vitro data indicates that the antidepressant action exerted by these compounds in vivo is mediated, at least in part, via interaction with serotonin receptors. The data presented here shows the valuable role that bromine plays in providing novel chemical space and electrostatic interactions. Bromine is ubiquitous in the marine environment and a common element of marine natural products.

Phytochemical composition, protective and therapeutic effect on gastric ulcer and α-amylase inhibitory activity of Achillea biebersteinii Afan.

Three sesquiterpene lactones [two germacranolides (micranthin and sintenin) and one guaianolide (4ß,10α-dihydroxy-5ß,7ß,8ßH-guaia-1,11(13)dien-12,8α-olide)] and four derivatives of 3-methoxy flavones (santin, quercetagetin-3,6,3'-trimethyl ether, quercetagetin-3,6-dimethyl ether, and 5,7 dihydroxy 3,3',4'-trimethoxy flavone) were isolated from the ethyl acetate extract (EAE) of the aerial parts of Achillea biebersteinii Afan. (Asteraceae). Evaluation of protective and therapeutic effects of EAE against ethanol-induced gastric ulcer in rats was carried. Antiulcer activity evaluation was done through measuring ulcer indices, stomach acidity, gastric volume and lesion counts. Oxidative stress markers; malondialdehyde, glutathione and superoxide dismutase were also estimated. The work was extended to determine the histopathological assessment of the stomach. Gastric ulcer exhibited a significant elevation of the ulcer index and oxidative stress markers. The extract attenuated these increments and recorded protective and therapeutic effects against gastric ulcer. Hyperglycaemia increases the mucosal susceptibility to ulcerogenic stimuli and predisposes gastric ulceration. In vitro α-amylase inhibitory assay was applied to evaluate the post prandial antihyperglycaemia activity. The result showing that the EAE has the ability to reduce starch-induced postprandial glycaemic excursions by virtue of potent intestinal α-amylase inhibitory activity. These findings demonstrated the remarkable potential of A. biebersteinii as valuable source of antiulcer agent with post prandial hyperglycaemia lowering effect.

Flavone composition and antihypercholesterolemic and antihyperglycemic activities of Chrysanthemum coronarium L.

Five flavones were isolated from Chrysanthemum coronarium L., four of which were isolated for the first time from the genus Chrysanthemum. Two were the flavonoid aglycones 5,7-dihydroxy-3,6,4'-trimethoxyflavone (1) and scutellarin-6,7-dimethyl ether (2). A new flavonoid glycoside, apigenin-7-O-[2"(6'''-O-beta-D-acetylglucopyranosyl)]-6"-O-acetylglucopyranoside (3), along with two known ones, i. e. apigenin-7-O-(2"-O-beta-D-glucopyranosyl)-beta-D-glucopyranoside (4) and 6-methoxy quercetin-7-O-beta-D-glucopyranoside (5), were identified. Structures were elucidated by NMR and MS. The therapeutic value of petroleum ether, ethyl acetate, and methanol extracts, respectively, in rats suffering from hypercholesterolemia--as a consequence of high-fat diet-and hyperglycemia--as a consequence of hypercholesterolemia and low doses of streptozotocin--was investigated through determination of biochemical markers and histopathology. The ethyl acetate and methanol extracts showed remarkable results, followed by the petroleum ether extract.

Preliminary in vitro and in vivo evaluation of antidiabetic activity of Ducrosia anethifolia Boiss. and its linear furanocoumarins.

Aim. Ducrosia anethifolia is used as flavoring additive. There have been little detailed phytochemical reports on this genus and the antidiabetic activity of this plant is not yet evaluated. Method. Structure of compounds was deduced by spectroscopic analyses. Preliminary in vitro evaluation of the antidiabetic activity of crude extract and its furanocoumarins was carried out ( α -amylase, α -glucosidase, and ß -galactosidase). The in vivo activity was investigated by measuring some oxidative stress markers. Biomarkers of liver injury and kidney were also determined. Results. Eight linear furanocoumarins, psoralen, 5-methoxypsoralen, 8-methoxypsoralen, imperatorin, isooxypeucedanin, pabulenol, oxypeucedanin methanolate, oxypeucedanin hydrate, and 3-O-glucopyranosyl- ß -sitosterol, were isolated. All compounds were reported for the first time from the genus Ducrosia except pabulenol. The blood glucose level, liver function enzymes, total protein, lipid, and cholesterol levels were significantly normalized by extract treatment. The antioxidant markers, glucolytic, and gluconeogenic enzymes were significantly ameliorated and the elevated level of kidney biomarkers in the diabetic groups was restored. The compounds showed inhibitory activity in a concentration dependant manner. Imperatorin and 5-methoxypsoralen showed the most potent inhibiting power. Conclusion. D. anethifolia extract showed hypoglycemic, hypolipidemic, and antioxidant effect as well as ameliorating kidney function. This extract and some linear furanocoumarins exhibited carbohydrate metabolizing enzymes inhibitory effect.