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This study aims to explore analgesic, antidiarrheal, neuropharmacological, and antibacterial activities of petroleum ether and water fractions of Justicia aurea (J. aurea). The results of analgesic activity showed that both nonpolar (petroleum ether) and polar (water) fractions of J. aurea extract at 250 and 500 mg/kg significantly suppressed the writhing reflex dose-dependently. Here, the potentiality of petroleum ether fraction was higher than that of water fraction. In the castor oil-induced diarrheal mice, both fractions of J. aurea extract, at 250 and 500 mg/kg, significantly delayed the onset of diarrhea and lessened the total number of feces in a dose-dependent manner. Of the two fractions, the nonpolar fraction was found to exhibit a better effect. Both fractions appreciably reduced the number of squares crossed by the mice at both 250 and 500 mg/kg. At 500 mg/kg, petroleum ether fraction reflected a slightly better effect than that of water fraction. In disc diffusion antibacterial assay, both fractions showed minor effects against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), however, only the water fraction exhibited low activity against Salmonella enterica (S. enterica). In conclusion, the nonpolar fraction of J. aurea. showed better analgesic, antidiarrheal, and CNS depression effects.

Moringa oleifera (Family- Moringaceae) is a well-known vegetable for its health benefits for thousands of years having diverse nutritional bioactive constituents. Phytochemical analysis of ethanolic extract of this plant indicated the presence of carbohydrate, reducing sugar, combined reducing sugar, glycosides, tannins (absent in seeds), alkaloids, flavonoids, saponins and steroids. In diuretic activity test, the extract showed a significant (p

The study was aimed to evaluate pharmacological activities of the leaves of Enhydra fluctuans Lour. (Family-Asteraceae). The interesting reported pharmacological activities, coupled with the use of the plant in traditional medicine qualify E. fluctuans Lour. for possible analgesic, antidiarrhoeal and antioxidant activities. These activities were investigated on animal model like Swiss albino mice. Phytochemical analysis using standard screening methods indicated the presence of alkaloids, tannins, steroids, gums, glycosides, saponins and flavonoids in the ethanolic plant extract. The ethanolic extract obtained by cold extraction method, showed anti oxidant activity of IC50 = 197 µgm/ml in DPPH assay while that of the standard ascorbic acid was observed to be IC50 = 18 µgm/ml. In Folin-Ciocalteau assay total phenolic content was found to be 157 mg GAE/100 gm of dry powder. This extract when applied at 250 and 500 mg/kg exhibits significant inhibition of writhing reflex 25.43% (p< 0.02) and 40.67 % (p< 0.05) respectively while with that of the standard drug diclofenac sodium inhibition was observed to be 68.82% (p

Sonneratia caseolaris is a widely distributed mangrove plant having much therapeutic importance in traditional medicine. This plant is reported for possessing numerous compounds that are already used for many therapeutic purposes. After finding the presence of antioxidant components in the qualitative antioxidative assay, we went to conduct quantitative tests where the total contents of phenolics, flavonoids, and tannins were estimated as 122 mg GAE/gm, 613 mg QE/gm, and 30 mg GAE/gm, respectively. In DPPH free radical, H2O2, and superoxide radical scavenging assay, the SC50 values were found to be 87, 66, and 192 μg/ml, respectively. In FeCl3 reducing power assay, the RC50 of SC extract and ascorbic acid were 80 and 28 μg/ml, respectively. This extract revealed a significant peripheral analgesic effect in the acetic acid-induced writhing model in mice by reducing the writhing impulse by about 21% and 39% at 250 and 500 mg/kg doses, respectively, and a central analgesic effect in the tail immersion method by elongating the time up to about 22% and 37% at the same doses. In the anti-inflammatory test in mice, this extract reduced the paw edema size over the observed period in a dose-dependent manner. It also showed a significant reduction in the elevated rectal temperature of mice in the observing period in Brewer’s yeast-induced pyrexia model. In silico analysis revealed better binding characteristics of ellagic acid and luteolin among other compounds with various receptors that might be responsible for antioxidative and anti-inflammatory properties. From our observation, we suppose that SC fruits might be a potential source of drug leads for various inflammatory disorders.

Plants are the major source of therapeutic compounds and have huge applications in Pharma Industry. To identify new sources of therapeutic compounds, we studied acute toxicity, antihyperglycemic, anti-inflammatory, and anticoagulant activities of the polar and nonpolar fractions of Justicia aurea (J. aurea). Our initial phytochemical screening of J. aurea exhibited the presence of numerous secondary metabolites such as reducing sugars, glycosides, tannins, gums, alkaloids, phenolic compounds, and carbohydrates which might be primarily responsible for its medicinal properties. In the acute toxicity test, the result showed no toxicity up to 2000 mg/kg. In the antihyperglycemic activity test, administration of petroleum ether fraction and water fraction of J. aurea extract to glucoseloaded mice at 250 and 500 mg/kg body weight (BW) reduced the blood glucose levels compared to control mice. Between two fractions, the water fraction was found to exhibit better potentiality at 500 mg/kg BW. In the anti-inflammatory assay, at 250 and 500 mg/kg water fraction exhibited anti-inflammation by 20.00% and 31.67%, respectively and petroleum ether fraction by 13.33% and 18.00%, respectively. In anticoagulant activity, the test indicated that water fraction has minor anticoagulant potentiality compared to control. In conclusion, the polar water fraction shows better medicinal properties than the nonpolar petroleum ether fraction of J. aurea.

This research work focuses on determining the antidiabetic and antioxidative properties of ethanolic extract of Heriteira fomes pneumatophores. The in vitro antioxidative activity was tested through several qualitative and quantitative assays which revealed the radical scavenging activity of this plant. The in vivo antihyperglycemic activity of plant extract was confirmed by the oral glucose tolerance test in the mice model. The antidiabetic potential was tested on streptozotocin-induced diabetic rats followed by measuring several hematological parameters and lipid profiles where the extract significantly affected those parameters. The results suggest that H. fomes pneumatophores might be a potential source of antioxidative and antidiabetic bioactive compounds. Dhaka Univ. J. Pharm. Sci. 20(3): 283-291, 2022 (June) Centennial Special Issue

Sonneratia caseolaris (L.) is a common mangrove plant which has significant medicinal value in traditional medicine. Ethanol extract from the fruits of S. caseolaris (SCE) was used in this project to explore its different pharmacological effects considering its traditional usage. In the castor oil-induced diarrheal method, SCE significantly lengthened the latency of the first defecation period up to 95.8 and 119.4 min as well as lowering stool count by 43.3% and 64.4% at the doses of 250 and 500 mg/kg, respectively. In evaluating the neuropharmacological effect using the open-field model, a significant central nervous system (CNS) depressant nature was observed after a reduction in the no. of squares crossed by mice at various time intervals. In evaluating the blood coagulation effect, SCE significantly reduced blood clotting time at 5.86, 5.52, and 5.01 min at 25, 50, and 100 mg/ml doses, respectively. In the assessment of the anthelmintic effect, SCE significantly killed Paramphistomum cervi (P. cervi) where the death times of the nematodes were 40.3, 36.8, and 29.9 min at 12.5, 25, and 50 mg/ml doses, respectively. The extract showed a very poor cytotoxic effect in brine shrimp lethality bioassay. In molecular docking analysis, maslinic acid, oleanolic acid, luteolin, luteolin 7-O-β-glucoside, myricetin, ellagic acid, and R-nyasol showed the best binding affinities with the selected proteins which might be the credible reasons for eliciting pharmacological responses. Among these seven compounds, only luteolin 7-O-β-glucoside had two violations in Lipinski’s rule of five.

Stenochlaena palustris is a widely found fern in mangrove forests and other areas of different countries over the world. This plant has many uses in traditional medicine of many countries. This study was conducted on its leaves extract to investigate its different phytochemical and pharmacological properties based on its local medicinal uses. Phytochemical screening indicated the presence of different secondary metabolites in this plant. On silica coated TLC plates, the extract exhibited the presence of different antioxidative compounds. Total phenolic, flavonoid and tannin contents were determined (97 mg GAE/g, 90 mg QE/g and 23 mg GAE/g, respectively). This extract also scavenged DPPH, hydrogen peroxide and superoxide radicals (SC50 = 80, 158 and 236 μg/ml, respectively). It also showed ferric ion reducing capability (RC50 =166 μg/ml). This plant showed significant antihyperglycemic, peripheral analgesic (acetic acid induced), anti-inflammatory (formaldehyde induced) and laxative activities in mice. This plant also showed little cytotoxic activity in brine shrimp lethality bioassay. These results are also compared with respective standard drugs and our findings justified its traditional usage.

Collected bark was extracted in ethanol and fractionated in different polar and nonpolar solvents, i.e., water, chloroform, ethyl acetate, andPhytochemical analysis indicated that alkaloids, tannins, flavonoids, saponins, glycosides, and terpenoids were detected in the most bioactive crude extracts, whereas alkaloids, terpenoids, saponins, and gums were found in bioactive

Ethanolic extracts of leaves and hypocotyls of a mangrove plant, Bruguiera gymnorrhiza (Family Rhizophoraceae), were investigated to identify the presence of different phytochemicals and to assess the antihyperglycemic, antidiarrheal, analgesic and antioxidative activity in the current study. Oral glucose tolerance test (OGTT) was performed to investigate the in vivo antihyperglycemic activity and leaves extract (LE) was found to possess significant antihyperglycemic property compared to hypocotyl extract (HE). Therefore, the leaves extract was considered for α-Glucosidase enzyme inhibitory activity test and substantial α-glucosidase enzyme inhibitory property was observed with an IC50 (concentration required to inhibit 50% enzyme) value of 2.670. Antioxidative activity of plant extracts was tested in vitro by evaluating their ability to scavenge DPPH, hydrogen peroxide and hydroxyl radical as well as superoxide anions. In all cases, LE showed greater activity than HE. In addition, LE demonstrated higher amount of total phenolics, flavonoids and tannins indicating higher antioxidant effect compared to HE. For the evaluation of antidiarrheal effect in castor oil induced diarrheal mice, both extracts showed significant inhibition of defecation at doses 250 and 500 mg/kg body weight. Finally, for acetic acid-induced writhing method to evaluate the analgesic activity, significant percentage inhibition of writhing (P

Introduction Ceriops decandra (CD) and Ceriops tagal (CT) are two traditionally used mangrove plants widely distributed along the coastal areas of South Asia, Africa, South Pacific. In this study, we evaluated the diuretic potential of aerial roots of CD, CT and assessed the effectiveness of the plants’ terpenoids enriched bioactive constituents against human carbonic anhydrase (hCA) enzyme through molecular docking. Materials and methods Firstly, the acute toxicity of CD and CT was evaluated in mice. In vivo diuretic activity was then studied in mice and the volume of excreted urine was measured. The urine was further examined for pH, density and Na+, K+, Cl− concentrations. From this, the saluretic, natriuretic, kaliuretic and CAI (carbonic anhydrase inhibitory) activities were calculated. Finally, total terpenoid contents (TTC) of the plant extracts were quantified and the terpenoids previously reported from both CD and CT were docked against four hCA isoforms - hCAII, hCAIV, hCAXII and hCAXIV. Results In the acute toxicity assessment, no sign of toxicity was found. In diuretic activity evaluation, both extracts displayed substantial increase in urine volume, with CD being at top. Concentrations of Na+, K+ and Cl− were also upsurged at a high dose of treatment (500 mg/kg). Both extracts at 500 mg/kg dose demonstrated potent saluretic, natriuretic and CAI activity. The TTC of CD was significantly higher than CT. In molecular docking analysis, greater binding affinity against hCA isoforms was demonstrated by the terpenoids reported from CD. Conclusion Aerial roots of both CD and CT possess substantial diuretic activity with an inhibitory effect on CA. Here, diuretic potential as well as the total terpenoid content of CD were much greater between the two.

The present study was designed to investigate different phytochemical groups present in ethanolic extract of Argemone mexicana aerial parts (EAMA) as well as to assess the analgesic, antidiarrheal, antibacterial, anthelmintic and cytotoxic activities of EAMA. Moreover, peripheral and central analgesic activities were evaluated by acetic acid-induced writhing test, formalin-induced paw licking test, tail immersion test and hot plate test. In vivo castor oil-induced diarrheal model and magnesium sulphate induced diarrheal model in mice were utilized for the assessment of antidiarrheal activity. Again, antibacterial activity was evaluated using disc diffusion assay. Anthelmintic activity was carried out on Paramphistomum cervi (Trematoda). Cytotoxic activity was assessed through brine shrimp lethality bioassay. The extract demonstrated the presence of alkaloids, flavonoids, phenolic compounds, tannins, glycosides and gums in phytochemical screening. In case of acetic acid-induced writhing and formalin induced paw licking test, both lower and higher doses of EAMA showed significant percentage inhibition of writhing as well as paw licking respectively (*P

Ethanolic extracts of pneumatophores of two mangrove species- Avicennia alba and Sonneratia apetala were studied in vitro for antioxidant capacity by measuring their ability to scavenge free radicals and determining total phenolic, flavonoid and tannin contents. In vivo measurement of antihyperglycemic activity of extracts was done by oral glucose tolerance test. In considering the antioxidant activity, S. apetala extract showed superior IC50 (concentration of sample required to inhibit 50% of free radicals) value for scavenging DPPH radical (71.77 μg/ml), hydrogen peroxide radical (97.27 mg/l), hydroxyl radical (79.62 mg/l) and superoxide anion (108.89 mg/l). For A. alba, the values for the radical scavenging assays were much higher. In addition, total phenol, flavonoid and tannin content demonstrated by S. apetala were 204.03 mgGAE/g, 228.68 mgQE/g and 235.89 mgGAE/g whereas for A. alba, they were 65.52 mgGAE/g, 44 mgQE/g and 37.71 mgGAE/g, respectively. In oral glucose tolerance test, S. apetala reduced the blood glucose level to a higher extent than A. alba. So, S. apetala with higher amount of secondary metabolites (phenol, flavonoid, tannin) is a superior source of natural antioxidants and antihyperglycemics. Dhaka Univ. J. Pharm. Sci. 17(2): 205-211, 2018 (December)

Sundarbans is the largest single block of tidal halophytic mangrove forest in the world and located in southern part...

This report describes the development of a target-protein-oriented natural-products-isolation (TPO-NAPI) method for Hedgehog inhibitors and the direct GLI1 inhibitor, 5′-O-methyl-3-hydroxyflemingin A (3), which inhibited hedgehog (Hh) signal transduction and diminished characteristics of cancer stem cells. Eight natural products (including three newly described products) that directly bind to GLI1 were rapidly obtained via the TPO-NAPI method developed using GLI1 protein-immobilized beads. 5′-O-Methyl-3-hydroxyflemingin A (3) inhibited Hh signaling (IC50 7.3 μM), leading to decreasing production of the Hh target proteins BCL2, PTCH1, and BMI1. 5′-O-Methyl-3-hydroxyflemingin A (3) was cytotoxic to Hh-related cancer cells. CD experiments revealed that 5′-O-methyl-3-hydroxyflemingin A (3) directly bound GLI1 (Kd = 7.7 μM). Moreover, 5′-O-methyl-3-hydroxyflemingin A (3) diminished cancer stem cell characters of Huh7 such as sphere formation and production of the cancer stem cell marker EpCAM. These results su...

Natural products isolation using protein based methods is an attractive for obtaining bioactive compounds. To discover neural stem cell (NSC) differentiation activators, we isolated eight inhibitors of Hes1 dimer formation from Psidium guajava using the Hes1-Hes1 interaction fluorescent plate assay and one inhibitor from Terminalia chebula using the Hes1-immobilized beads method. Of the isolated compounds, gallic acid (8) and 4-O-(4”-O-galloyl-α-L-rhamnopyranosyl)ellagic acid (11) showed potent Hes1 dimer formation inhibitory activity, with IC50 values of 10.3 and 2.53 μM, respectively. Compound 11 accelerated the differentiation activity of C17.2 NSC cells dose dependently, increasing the number of neurons with a 125% increase (5 μM) compared to the control.

The Ethanol extract of leaves of Diospyros blancoi (Ebenaceae) was tested for its pharmacological and antioxidant activities. Acetic acid induced writhing method, Brine shrimp lethality bioassay and disc diffusion method were applied for determining analgesic, cytotoxic and antibacterial activity, respectively. To investigate antioxidant activity, 2, 2-diphenyl-1-picryl-hydrazil (DPPH) free radical scavenging, total phenolic and flavonoid contents were applied. The extract produced dose-dependent analgesic activity in acetic acid-induced writhing test. Significant antibacterial and cytotoxic activity were also observed. In DPPH radical scavenging assay, the extract showed the IC50 value of 59 µg/mL (Ascorbic acid, 17 µg/mL). Total phenolic and flavonoids contents were 62.54 mg GAE and 9.63 mg QE/g of dry powder, respectively. In HPLC analysis, Catechin hydrate, Rutin hydrate, Vanillic acid, p-coumaric acid, and Quercetin were detected in the extract (39.51, 20.67, 1.68, 1.52, 1.08 mg/100 g of dry extract, respectively). Presence of polyphenolic compounds in the extract might have attributed towards the observed bio-activity.

Four alkaloids, voacangine (1), isovoacangine (2), coronaridine (3), and coronaridine hydroxyindolenine (4), were isolated from the MeOH extract of Tabernaemontana divaricata aerial parts by activity-guided fractionation for Wnt signal inhibitory activity. Compounds 1-4 exhibited TCF/β-catenin inhibitory activities with IC50 values of 11.5, 6.0, 5.8, and 7.3 μM, respectively. Of these, coronaridine (3) decreased β-catenin levels in SW480 colon cancer cells, while this decrease in β-catenin was not suppressed by a co-treatment with 3 and MG132, a proteasome inhibitor. These results suggested that the decrease observed in β-catenin levels by coronaridine (3) did not depend on a proteasomal degradation process. On the other hand, the treatment of SW480 cells with coronaridine (3) caused a decrease in β-catenin mRNA levels. Thus, coronaridine (3) may inhibit the Wnt signaling pathway by decreasing the mRNA expression of β-catenin.

The ability of TRAIL to selectively induce apoptosis in cancer cells while sparing normal cells makes it an attractive target for the development of new cancer therapy. In search of bioactive natural products for overcoming TRAIL-resistance from natural resources, we previously reported a number of active compounds. In our screening program on natural resources targeting overcoming TRAIL-resistance, activity-guided fractionations of the extract of Xanthium strumarium led to the isolation of five sesquiterpene compounds (1-5). 11α,13-dihydroxanthinin (2) and 11α,13-dihydroxanthuminol (3) were first isolated from natural resources and xanthinosin (1), desacetylxanthanol (4), and lasidiol p-methoxybenzoate (5) were known compounds. All compounds (1-5) showed potent TRAIL-resistance overcoming activity at 8, 20, 20, 16, and 16 μM, respectively, in TRAIL-resistant AGS cells. Compounds 1 and 5 enhanced the levels of apoptosis inducing proteins DR4, DR5, p53, CHOP, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 and also decreased the levels of cell survival protein Bcl-2 in TRAIL-resistant AGS cells in a dose-dependent manner. Compound 1 also enhanced the levels of DR4 and DR5 proteins in a time-dependent manner. Thus, compounds 1 and 5 were found to induce both extrinsic and intrinsic apoptotic cell death. Compound 1 also exhibit TRAIL-resistance overcoming activity in DLD1, DU145, HeLa, and MCF7 cells but did not decrease viability in non-cancer HEK293 cells up to 8 μM.

The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels.

The inhibition of the hedgehog (Hh) signaling pathway has emerged as an attractive anti-cancer strategy. As part of our continuing search for natural inhibitors of the Hh/GLI1 signaling pathway, we isolated three alkaloids (1-3) from Crinum asiaticum. Compounds 1 and 3 showed potent Hh/GLI1-mediated transcriptional inhibitory activity and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compounds 1 and 3 clearly inhibited the Hh signaling pathway by down-regulating the expression of GLI-related proteins (PTCH and BCL2) in DU145 cells.

Scopadulciol (1), a scopadulan-type diterpenoid, was isolated from Scoparia dulcis along with three other compounds (2-4) by an activity-guided approach using the TCF reporter (TOP) luciferase-based assay system. A fluorometric microculture cytotoxicity assay (FMCA) revealed that compound 1 was cytotoxic to AGS human gastric adenocarcinoma cells. The treatment of AGS cells with 1 decreased β-catenin levels and also inhibited its nuclear localization. The pretreatment of AGS cells with a proteasome inhibitor, either MG132 or epoxomicin, protected against the degradation of β-catenin induced by 1. The 1-induced degradation of β-catenin was also abrogated in the presence of pifithrin-α, an inhibitor of p53 transcriptional activity. Compound 1 inhibited TOP activity in AGS cells and downregulated the protein levels of cyclin D1, c-myc, and survivin. Compound 1 also sensitized AGS cells to tumor necrosis factor-related apoptosis ligand (TRAIL)-induced apoptosis by increasing the levels of the death receptors, DR4 and DR5, and decreasing the level of the antiapoptotic protein Bcl-2. Collectively, our results demonstrated that 1 induced the p53- and proteasome-dependent degradation of β-catenin, which resulted in the inhibition of TCF/β-catenin transcription in AGS cells. Furthermore, 1 enhanced apoptosis in TRAIL-resistant AGS when combined with TRAIL.

A B S T R A C T The Wnt signal regulates various biological processes, and its aberrant activation is associated with the development of diseases. Thus, inhibiting the Wnt signal provides a promising strategy to treat these diseases. Our cell-based luciferase assay system, which targets the Wnt signal (TOP assay), revealed that Azadirachta excelsa inhibited the Wnt signal. The activity-guided isolation of the MeOH fruit extract of A. excelsa provided one new (1) and seven known (2–8) limonoids. Their structures were elucidated based on their spectroscopic data, and their NMR data were compared with those in the literature. Compounds 3–6 potently inhibited the Wnt signal with IC50 values of 127 nM, 300 nM, 252 nM, and 121 nM, respectively. Compound 4 exhibited selective cytotoxicity against AGS and HCT116. Western blot analysis showed that 4 did not affect the level or localization of b-catenin, but downregulated the level of c-myc. Our results suggested that 4 may have inhibited the Wnt signal by affecting the components downstream of b-catenin.

Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease occur due to loss of the structure and function of neurons. For the potential treatment of neurodegenerative diseases, accelerators of neuronal differentiation of neural stem cells (NSCs) have been focused on and a cell-based assay system for measuring Notch signaling pathway activity was constructed. Using this assay system, eight compounds isolated from Calotropis gigantea were identified as inhibitors of the Notch signaling pathway. Hes1 and Hes5 are target genes of the Notch signaling pathway, and compound 1, called uscharin, decreased the protein levels of Hes1 and Hes5 in assay cells and MEB5 cells (mouse NSCs). Furthermore, uscharin (1) enhanced the differentiation of MEB5 cells into neurons. The mechanism of uscharin (1) for the Notch signaling inhibitory activity would be acceleration of the degradation of the Notch intracellular domain (NICD) in the MEB5 cells.

Wnt signaling plays important roles in proliferation, differentiation, development of cells, and various diseases. Activity-guided fractionation of the MeOH extract of the Ricinus communis stem led to the isolation of four compounds (1-4). The TCF/β-catenin transcription activities of 1 and 3 were 2.2 and 2.5 fold higher at 20 and 30μM, respectively. Cells treated with ricinine (1) had higher β-catenin and lower of p-β-catenin (ser 33, 37, 45, Thr 41) protein levels, whereas glycogen synthase kinase 3β (GSK3β) and casein kinase 1α (CK1α) protein levels remained unchanged. Cells treated with pyrvinium, an activator of CK1α, had lower β-catenin levels. However, the combined treatment of pyrvinium and 1 led to higher β-catenin levels than those in cells treated with pyrvinium alone, which suggested that 1 inhibited CK1α activity. Furthermore, 1 increased β-catenin protein levels in zebrafish embryos. These results indicated that 1 activated the Wnt signaling pathway by inhibiting CK1α.

Wnt signaling plays key roles in embryonic development and various human diseases. Activity-guided testing to isolate Wnt signaling inhibitors from the methanol extract of Calotropis gigantea (Asclepiadaceae) exudutes identified six Wnt inhibitory cardenolides (1-6), of which 1, 3, 5, and 6 exhibited potent TCF/β-catenin inhibitory activities (IC50 0.7-3.6 nM). Calotropin (1) inhibited Wnt signaling by decreasing both nuclear and cytosolic β-catenin in a dose-dependent manner, and promoted degradation of β-catenin by increasing the phosphorylation of β-catenin at Ser45 through casein kinase 1α (CK1α). Moreover, 1 significantly increased CK1α protein and mRNA levels. The results suggest that 1 inhibits the Wnt signaling pathway by increasing CK1α protein levels. To the best of our knowledge, calotropin is the first small molecule to increase CK1α levels.

Various literatures recorded approximately 60 medicinal plants in Bangladesh that have antidiabetic properties. Of these medicinal plants, only 14–16 are found in traditional herbal markets and they are being randomly used to treat diabetes. Since diabetes mellitus increases reactive free radicals along with various complications in the body, antidiabetic plants that can potentially neutralize free radicals, may be of central interest to manage the disease. Present study compares functional bioactive components such as total phenolics, flavonoids, anthocyanins contents and antioxidant potential of methanol extracts of antidiabetic medicinal plants that are common in traditional herbal markets. Among the 14 extracts, Syzygium cumini was very rich in total polyphenol content (294 mg gallic acid equivalent, GAE/g) followed by Swertia chirata (183 mg GAE/g) and Ficus racemosa (bark) (154 mg GAE/g). These three extracts also had elevated amount of flavonoids and anthocyanins. S. cumini showed very high DPPH and NO free radical scavenging activities with IC50 of 6.25 and 48.61 μg/mL respectively followed by S. chirata and F. racemosa (bark). S. cumini also showed very high reducing power and total antioxidant capacity followed by S. chirata and F. racemosa (bark). In addition, the study revealed strong correlation between phenolics and reducing power (r = 0.94). Hence, among the 14 extracts, S. cumini, S. chirata and F. racemosa (bark) are potential sources of antioxidant agents. Therefore, these three medicinal plants have diverse beneficial effects on physiological health and they might be the choice of plants to treat diabetes.

In a screening program for natural products that can overcome TRAIL resistance, a new eudesmane-type sesquiterpenoid (1), three new guaianolides, mehirugins A-C (2-4), and two known guaianolides (5 and 6) were isolated from a MeOH extract of Kandelia candel leaves. Compounds 1 and 3-6 in combination with TRAIL showed cytotoxic activity in sensitizing TRAIL-resistant human gastric adenocarcinoma cells.

The results revealed that different fractions of Commelina diffusa Burm. f. produced significant (p < 0.001, p < 0.01, p < 0.05, p < 0.02 and p < 0.5) inhibitory activity against the test bacteria and fungi. Methanolic fraction produced the highest zone of inhibition against the test bacteria (11 to 19 mm) which was followed by diethyl etheric extract (3 to 9 mm) and petroleum etheric extract (1 to 2 mm). Again, the methanolic extract showed the highest activity (the lowest MICs; 15.62 to 62.5 μg/μl) against seven species among the 11. In case of diethyl etheric and petroleum etheric fractions MICs were found to be (15.62 to 125 μg/μl) and (31.25 to 500 μg/μl), respectively. The diethyl etheric fraction showed the highest zone of inhibition against the fungi (15 to 19 mm) which was followed by methanolic extract (12 to 19 mm) and petroleum etheric extract (1 to 9 mm). Against the fungi the diethyl etheric extract showed the highest activity (i.e. the lowest MICs; 15.62 to 31.25 μg/μl). In case of methanolic and petroleum etheric fractions minimum inhibitory concentrations were found to be (15.62 to 125 μg/μl) and (31.25 to 250 μg/μl), respectively.

The inhibition of the Hedgehog (Hh) signaling pathway has emerged as an anti-cancer strategy. Three flavonoid glycosides including 2 new compounds (1-2) were isolated from Excoecaria agallocha as Hedgehog/GLI1-mediated transcriptional inhibitors and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compound 1 clearly inhibited the expression of GLI-related proteins (PTCH and BCL-2) and blocked the translocation of GLI1 transcription factors into the nucleus in PANC1. Deleting the Smoothened (Smo) function in PANC1 treated with 1 led to downregulation of the mRNA expression of Ptch. This study describes the first Hh signaling inhibitor which blocks GLI1 movement into the nucleus without interfering with Smo.

Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2–3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations. Copyright © 2010 John Wiley & Sons, Ltd.

A new monoterpene glycoside (1) isolated from the aerial part of Sibirae angustata RCHD. (Rosaceae) was found to be 1-O-beta-D-glucopyranosyl-geraniol-5,10-olide and named as sibiskoside. Acute toxicity study revealed that oral administration of 1 (2.5 g/kg body weight) to mice resulted in no death and no evidence of abnormalities in internal organs. Its oral administration to the mice reared with high-fat diet resulted in weight-loss, which was also reflected in serum triglyceride and sugar level, and the weight of abdominal fat. Sibiskoside could be considered to be an active ingredient of Liucha for exerting weight-loss effect in a drink of S. angustata.

An androstanoid, hoyasterone (1), a sesquiterpene, 15-bulnesolic acid (2), and a phenolic compound, 1-(4-hydroxy-3-methoxyphenyl)-1-methoxypropan-2-ol (3), together with a known triterpene, dihydrocanaric acid, were isolated from Hoya parasitica. Structures were elucidated by 1 D and 2 D NMR and mass spectroscopic analysis. Among the isolated compounds, only dihydrocanaric acid exhibited growth inhibitory activity against both HeLa and SW480 cells.

Nine sesquiterpenes and eight flavonoids were isolated from Zingiber spectabile for the first time. Structures were determined by spectroscopic methods. The major compound zerumbone (1) was found to be the most active (IC(50) 13 microg mL(-1)) in cell growth inhibitory assay against colon carcinoma SW480 cells.

Secoiridoid glucosides, 2″-epifraxamoside and demethyl-2″-epifraxamoside, and the secoiridoid, jasminanhydride were isolated from Jasminum grandiflorum together with four previously known phenolics and a triterpene. Structures were elucidated by detailed spectroscopic analysis. Stereochemistry of the compounds was determined by differential NOE experiment.

The ethanol extract of leaves of the mangrove Aegiceras corniculatum Blanco (Myrsinaceae) was screened for its antinociceptive, antidiarrhoeal and cytotoxic activities. The extract produced significant writhing inhibition in acetic acid-induced writhing in mice at the oral dose of 250 and 500 mg/kg body weight (P 10 mg/ml). The overall results tend to suggest the antinociceptive, antidiarrhoeal and cytotoxic activities of the extract.