Could dual G-protein coupling explain [d-Met]FMRFamide's mixed action in vivo?

In vitro studies have demonstrated that FMRFamide-related peptide receptors can be coupled to different G-proteins, mediating opposite stimulatory and inhibitory effects. The present study tested whether this duality might extend to effects in vivo. Antinociception in mice of ICV [d-Met²]FMRFamide, which produced agonist [ED₅₀ = 36.3 μg (61.6 nmol)] and antagonist [ID₅₀ = 0.72 μg (1.22 nmol)] actions, was attenuated by 24-h pretreatment with ICV pertussis toxin (ID₅₀ = 0.55 μg) or cholera toxin (ID₅₀ = 0.09 μg), suggesting that [d-Met²]FMRFamide in vivo effects might also be explained by dual coupling.     

Effect of cyclic analogues of valproic acid on glutamic acid decarboxylase activity as determined by different methods

In order to study the anticonvulsant activity of cyclic analogues of valproic acid, the effects of sodium valproate, sodium spiro (4:6) undecane-2-carboxylate, and sodium spiro (4:6) undecane-2-acetate were observed on the L-glutamic acid decarboxylase (GAD) activity of E. coli and C. welchii by radioisotopic, volumetric, and gravimetric methods. The results indicated that these compounds potentiated enzyme activity at low concentrations but higher concentrations exhibited an inhibitory effect. Fifty percent enzyme inhibition (ID_5O) ranges were 200–250 μg/ml, 50–75 μg/ml, and 150–200 μg/ml, for the three compounds respectively as determined by the radioisotopic method. While the radioisotopic was used as a conventional method, the microvolumetric and microgravimetric methods were developed for the first time and found to be applicable in determining the effect of the compounds on enzyme activity. The advantages of the latter two methods are that they are simple, safe, and inexpensive as compared to the radioisotopic method. The results by these methods indicated that the second compound was the strongest inhibitor of GAD activity.     

Phytochemical,Antiplasmodial, Cytotoxic and Antimicrobial Evaluation of a Southeast Brazilian Brown Propolis Produced by Apis mellifera Bees

Seven phenolic compounds (ferulic acid, caffeic acid, 4-methoxycinnamic acid, 3,4-dimethoxycinnamic acid, 3-hydroxy-4-methoxybenzaldehyde, 3-methoxy-4-hydroxypropiophenone and 1-O,2-O-digalloyl-6-O-trans-p-coumaroyl-β-D-glucopyranoside), a flavanonol (7-O-methylaromadendrin), two lignans (pinoresinol and matairesinol) and six diterpenic acids/alcohol (19-acetoxy-13-hydroxyabda-8(17),14-diene, totarol, 7-oxodehydroabietic acid, dehydroabietic acid, communic acid and isopimaric acid) were isolated from the hydroalcoholic extract of a Brazilian Brown Propolis and characterized by NMR spectral data analysis. The volatile fraction of brown propolis was characterized by CG-MS, composed mainly of monoterpenes and sesquiterpenes, being the major α-pinene (18.4 %) and β-pinene (10.3 %). This propolis chemical profile indicates that Pinus spp., Eucalyptus spp. and Araucaria angustifolia might be its primary plants source. The brown propolis displayed significant activity against Plasmodium falciparum D6 and W2 strains with IC₅₀ of 5.3 and 9.7 μg/mL, respectively. The volatile fraction was also active with IC₅₀ of 22.5 and 41.8 μg/mL, respectively. Among the compounds, 1-O,2-O-digalloyl-6-O-trans-p-coumaroyl-β-D-glucopyranoside showed IC₅₀ of 3.1 and 1.0 μg/mL against D6 and W2 strains, respectively, while communic acid showed an IC₅₀ of 4.0 μg/mL against W2 strain. Cytotoxicity was determined on four tumor cell lines (SK-MEL, KB, BT-549, and SK-OV-3) and two normal renal cell lines (LLC-PK1 and VERO). Matairesinol, 7-O-methylaromadendrin, and isopimaric acid showed an IC₅₀ range of 1.8–0.78 μg/mL, 7.3–100 μg/mL, and 17–18 μg/mL, respectively, against the tumor cell lines but they were not cytotoxic against normal cell lines. The crude extract of brown propolis displayed antimicrobial activity against C. neoformans, methicillin-resistant Staphylococcus aureus, and P. aeruginosa at 29.9 μg/mL, 178.9 μg/mL, and 160.7 μg/mL, respectively. The volatile fraction inhibited the growth of C. neoformans at 53.0 μg/mL. The compounds 3-hydroxy-4-methoxybenzaldehyde, 3-methoxy-4-hydroxypropiophenone and 7-oxodehydroabietic acid were active against C. neoformans, and caffeic and communic acids were active against methicillin-resistant Staphylococcus aureus.     

Stimulation and inhibition of neoplastic cell growth by tumor promoter-treated macrophages

Macrophages treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent inflammatory and tumor-promoting agent, can have the diametrically opposed functions of contact-mediated tumor cytotoxicity and release of soluble clonal proliferation factor(s) for tumor cells. In vitro TPA treatment of macrophages at 1.0 ng/ml induced prostaglandin E₂ release and morphological changes analogous to cell activation. In addition, conditioned medium from macrophages pulsed with TPA enhanced M109 carcinoma colony formation in vitro. Although macrophages were not rendered tumoricidal by TPA in vitro, cytotoxic macrophages were recovered from mice following ip treatment with TPA at 1–100 μg/kg. This indicated an indirect pathway for the activation of macrophages by TPA. The very weak tumor promoting 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate lacked effects on macrophages at all doses tested. The possibility that macrophage secretions (e.g., prostaglandin E₂, angiogenesis-stimulating factor(s), and clonal proliferation factor(s) for carcinogen-triggered cells) may be involved in the tumor promotion process is discussed.     

Antimicrobial activity and mechanism of action of Nu-3, a protonated modified nucleotide

For centuries, plants have been used in traditional medicines and there has been recent interest in the chemopreventive properties of compounds derived from plants. In the present study, we investigated the antibutyrylcholinestrasic (anti-BuChE) and antioxidant (against some free radicals) activities of extracts from Rhus pentaphyllum. Aqueous extracts were prepared from powdered R. pentaphyllum roots, leaves and seeds and characterized for the presence of tannins, flavonoids and coumarins. Seeds aqueous extract contained the highest quantities of both flavonoids and tannins (21.12% and 17.45% respectively). In the same way, seeds extracts displayed remarkable inhibition against BuChE over 95%, at 100 μg/ml and with IC₅₀ 0.74 μg/ml. In addition, compared to leaves and roots extracts, seeds aqueous extract revealed relatively strong antiradical activity towards the ABTS ^.+ (IC₅₀ = 0.25 μg/ml) and DPPH (IC₅₀ = 2.71 μg/ml) free radicals and decreased significantly the reactive oxygen species such O₂ ^.- (IC₅₀ = 2.9 μg/ml) formation evaluated by the non-enzymatic generating O₂ ^.- system (Nitroblue tetrazolium/riboflavine). These data suggest that the anti-BuChE activities mechanism of these extracts occurs through a free radical scavenging capacities. The present study indicates that extracts of Rhus pentaphyllum leaves, seeds and roots are a significant source of compounds, such as tannins, flavonoids and coumarins, with anti-BuChE and antioxidant activities, and thus may be useful for chemoprevention.     

Syntheses of Diastereoisomers of the Recent Pyrethroids,Fenvalerate (S-5602) and Cypermethrin (NRDC-149) from (–)-3-Phenoxy-mandelic Acid and Determination of Their Absolute Configurations

Lipopeptin A is a selective inhibitor of in vitro peptidoglycan synthesis of E. coli Y-10. In the study here it inhibited the formation of lipid intermediates from UDP-[U-¹⁴C]GlcNAc and UDP-MurNAc-l-Ala-d-Glu-meso-DAP-d-Ala-d-Ala, but did not inhibit the formation of MurNAc-pentapeptide-p-p-lipid from UDP-MurNAc-l-Ala-d-Glu-[³H]meso-DAP-d-Ala-d-Ala. Lipopeptin A also did not have a significant effect on polymerase reaction. Therefore, the inhibition of the formation of GleNAc-MurNAc-pentapeptide-p-p-lipid from MurNAc-pentapeptide-p-p-lipid and UDP-GlcNAc is concluded to be the site of action.

Lipopeptin A inhibits fungal growth, causing swelling in mycelia. It did not significantly inhibit the incorporations of ¹⁴C-labeled glucosamine, thymidine, uridine, phenylalanine, and sodium acetate into TCA insoluble fraction of mycelial suspension of Piricularia oryzae. In in vitro test, however, it inhibited the transfer of mannose from GDP-[U-¹⁴C]mannose (ID_5O = 250 μg/ml) and GlcNAc from UDP-[U-¹⁴C]GlcNAc (ID₅₀ = 100 μg/ml) into proteoheteroglycan with a particulate enzyme of Piricularia oryzae. It also slightly inhibited chitin synthesis (ID₅₀ = 750 μg/ml) in the same enzyme system, but did not inhibit β-l,3-glucan synthesis.     

Anti-inflammatory and anti-tumor-promoting effects of 5-deprenyllupulonol C and other compounds from Hop (Humulus lupulus L.)

A new phloroglucinol derivative, 5‐deprenyllupulonol C ( 1 ), along with four other phloroglucinol derivatives, 2 – 5 , five chalcones, 6 – 10 , four flavanones, 11 – 14 , two flavonol glycosides, 15 and 16 , and five triterpenoids, 17 – 21 , were isolated from the female inflorescence pellet extracts of hop (Humulus lupulus L.). Upon evaluation of these compounds against the Epstein? Barr virus early antigen (EBV‐EA) activation induced by 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) in Raji cells, twelve compounds, i.e., 1 – 4, 11 – 14, 17 – 19 , and 21 , showed potent inhibitory effects on EBV‐EA induction, with IC₅₀ values in the range of 215–393 mol ratio/32 pmol TPA. In addition, eleven compounds, i.e., 1 – 4, 6, 11, 12, 14, 17, 18 , and 20 , were found to inhibit TPA‐induced inflammation (1 μg/ear) in mice, with ID₅₀ values in the range of 0.13–1.06 μmol per ear. Further, lupulone C ( 2 ) and 6‐prenylnaringenin ( 14 ) exhibited inhibitory effects on skin‐tumor promotion in an in vivo two‐stage mouse‐skin carcinogenesis test based on 7,12‐dimethylbenz[a]anthracene (DMBA) as initiator and with TPA as promoter.     

Announcement: VIth winter prostaglandin conference

Prostaglandin production by methylcholanthrene-transformed 3T3 mouse fibroblasts (MC5-5), human normal fibroblasts (D550), and canine kidney (MDCK) cells was inhibited by several analogues of anthracene, phenanthrene, and benzoflavone. Among the most effective inhibitors of MC5-5's prostaglandin production were anthracene (ID₅₀=1.7 μM), 9,10-diaminophenanthrene (ID₅₀=0.48 μM), and 7,8-benzoflavone (ID₅₀=0.55 μM). Under identical conditions, the ID₅₀'s for indomethacin and aspirin were 0.049 and 8.9 μM respectively. Production of radioactive prostaglandins by MC5-5 cells from tritiated phospholipids was blocked by 7,8-benzoflavone, but not the release of radioactive arachidonic acid.     

Stimulation of human T-lymphocyte chemokinesis by arachidonic acid.

The migration of human T lymphocytes, assessed in modified Boyden chambers, was chemokinetically stimulated by arachidonic acid in a dose-related manner that achieved a peak level of 127 ± 34% enhancement (mean ± SD) at 8 μM arachidonic acid. The chemokinetic effect was dependent on the metabolism of the arachidonic acid by the T lymphocytes as derivatives of arachidonic acid that do not serve as prostaglandin and thromboxane precursors were without effect, while the cyclo-oxygenase inhibitors indomethacin (ID₅₀ = 10 μM) and 5,8,11,14-eicosatetraynoic acid (ETYA) (ID₅₀ = 20 μM) suppressed the stimulation of migration by arachidonic acid. The cyclo-oxygenase product 12-l-hydroxy-5,8,10-heptadecatrienoic acid (HHT) reproduced part of the chemokinetic effect of arachidonic acid, but the lipoxygenase product 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) as well as PGE₂, PGF_2α, and thromboxane B₂ had no stimulatory activity. The ability of ETYA, but not indomethacin, to suppress the migration of unstimulated T lymphocytes suggested that a lipoxygenase metabolite of endogenous arachidonic acid contributes to the maintenance of their normal levels of spontaneous migration.     

Selective inhibition of platelet lipoxygenase by baicalein

The effects of various flavonoids on platelet lipoxygenase and cyclooxygenase activities were studied. Baicalein selectively inhibited platelet lipoxygenase. The concentration for 50% inhibition (ID₅₀) was 0.12 μM for platelet lipoxygenase and 0.83 mM for platelet cyclooxygenase. Therefore, the ID₅₀ value for the cyclooxygenase was 6917 times that for the lipoxygenase. Baicalin also selectively inhibited the lipoxygenase, but it was less potent (ID₅₀=100 μM). Other flavonoids tested had no inhibitory effect on either enzyme.     

Three New 2,2′-Difurylketone Derivatives and Two New Chromones from the Rehmanniae Radix Praeparata

Rehmanniae Radix Praeparata is the processed products of the root of Rehmannia glutinosa. It has been used as a Traditional Chinese Medicine for thousands of years, and it has been found to possess widely pharmacological activities. In this study, three new 2,2′-difurylketone derivatives (rehmanniaeketone A–C) and two new chromones [3,8-dihydroxy-2-(2-hydroxyethyl)chromone and 3,8-dihydroxy-2-[(2-O-α-D-galactopyranosyloxy)ethyl]chromone] were isolated from the Rehmanniae Radix Praeparata. Furthermore all of the compounds were subjected to cytotoxic testing against the human lung carcinoma A549 cells. The cytotoxic results showed that rehmanniaeketone B and rehmanniaeketone C exhibited more stronger inhibition effects on the cell activity of A549 cells with the IC₅₀ 5.23 μM and 2.05 μM than other compounds. And 3,8-dihydroxy-2-(2-hydroxyethyl)chromone exhibited moderately inhibitory activity with the IC₅₀ 61 μM. Rehmanniaeketone A and 3,8-dihydroxy-2-[(2-O-α-D-galactopyranosyloxy]chromone showed no inhibitory effects.     

Synthesis and anti-tumor activities of methyl 2-O-aryl-6-O-aryl′-d-glucopyranosides

A synthetic method of introducing bulky aryl groups at the 2-O- and 6-O-positions on glucopyranosides was developed. A total of 37 new compounds of this class were obtained successfully. These compounds were tested on several tumor cell lines by MTT assays, and some of them exhibited encouraging inhibitory activities. The most potent compound, CAB-SHZH-27, exhibited EC₅₀ values of 14, 12, and 10 μmol/L on A549, MDA-MB-231 and HeLa cells, respectively. A preliminary structure–activity relationship analysis indicates that the two free hydroxyl groups on the d-glucose core are indispensable for the biological activities of this class of compounds, and the aryl group at the 6-O-position has a more obvious impact than the one at the 2-O-position. An interesting ‘on–off’ mechanism of this class of compounds was also observed in our MTT assays, which remains to be explored.     

Biotransformation pathway and kinetics of the hydrolysis of the 3-O- and 20-O-multi-glucosides of PPD-type ginsenosides by ginsenosidase type I

Ginsenosidase type I from Aspergillus niger g.48 can hydrolyze the 3-O- and 20-O-multi-glycosides of PPD-type ginsenosides. The enzyme molecular weight is approximately 74 kDa. When hydrolyzing the glycosides of Rb1, Rb3, Rb2 and Rc, the structures of which only differ in their terminal 20-O-glycosides, ginsenosidase type I hydrolyzes both the 3-O- and 20-O-glycosides of Rb1 and Rb3 using two pathways, but the enzyme first hydrolyzes the 3-O-glucosides of Rb2 and Rc using one pathway. One pathway of Rb1 hydrolyzes the 20-O-Glc of Rb1 to Rd→F2→C-K; another pathway hydrolyzes the 3-O-Glc of Rb1 to Gyp17→Gyp75→C-K. Two hydrolysis pathways are used to hydrolyze the 20-O-Xyl and the 3-O-Glc of Rb3. According to the enzyme reaction parameters K_m, V_max and V₀ at a 10 mM substrate concentration, the enzyme hydrolysis velocity values decrease in the following order: the 20-O-Xyl of Rb3→Rd> the 20-O-Glc of Rb1→Rd> the 3-O-Glc of Rc> the 3-O-Glc of Rb2> the 3-O-Glc of Rd> the 3-O-Glc of Rb3→C-Mx1> the 3-O-Glc of Rb1→Gyp17> the 3-O-Glc of F2> the 3-O-Glc of 20(S)-Rg3.     

4-O-methylhonokiol attenuated β-amyloid-induced memory impairment through reduction of oxidative damages via inactivation of p38 MAP kinase

Oxidative stress induced neuronal cell death by accumulation of β-amyloid (Aβ) is a critical pathological mechanism of Alzheimer's disease (AD). Intracerebroventrical infusion of Aβ_1-42 (300 pmol/day per mouse) for 14 days induced neuronal cell death and memory impairment, but pre-treatment of 4-O-methylhonokiol (4-O-MH), a novel compound extracted from Magnolia officinalis for 3 weeks (0.2, 0.5 and 1.0 mg/kg) prior to the infusion of Aβ_1-42 and during the infusion dose dependently improved Aβ_1-42-induced memory impairment and prevented neuronal cell death. Additionally, 4-O-MH reduced Aβ_1-42 infusion-induced oxidative damages of protein and lipid but reduced glutathione levels in the cortex and hippocampus. Aβ_1-42 infusion-induced activation of astrocytes and p38 mitogenic activated protein (MAP) kinase was also prevented by 4-O-MH in mice brains. In further study using culture cortical neurons, p38 MAP kinase inhibitor abolished the inhibitory effect of 4-O-MH (10 μM) on the Aβ_1-42 (5 μM)-induced reactive oxidative species generation and neuronal cell death. These results suggest that 4-O-MH might prevent the development and progression of AD through the reduction of oxidative stress and neuronal cell death via inactivation of p38 MAP kinase pathway.     

Separation of the glucuronides of entacapone and its (Z)-isomer in urine by micellar electrokinetic capillary chromatography

A micellar electrokinetic capillary chromatography (MECC) method was developed for the separation of the 3-O-glucuronides of entacapone and its (Z)-isomer, the two main urinary metabolites of entacapone in humans. Entacapone is a novel, potent inhibitor of catechol-O-methyltransferase (COMT) intended for use as an adjunct in the treatment of Parkinson’s disease. Urine samples spiked with synthetic 3-O-glucuronides were used to study the effects of running buffer pH, composition and applied voltage on separation of the closely migrating glucuronides. The 3-O-glucuronide of nitecapone, was used as internal standard. The greatest improvement in separation was achieved by increasing the running buffer ionic concentration. Changes in pH had little effect on the separation, whereas increase in sodium dodecyl sulfate (SDS) concentration slightly improved resolution. Baseline separation and good selectivity relative to urine components were achieved by using a phosphate (25 mM)–borate (50 mM)–SDS (20 mM) running buffer, pH 7.0, in a 75 μm×60/67 cm fused-silica capillary at 15 kV and a 335 nm cut-off filter in the UV detector. The limits of detection (LOD) at a signal-to-noise ratio of 3 were about 0.25 μg/ml (5.2·10 ⁻⁷M) (injection 0.5 p.s.i./8 s). The linear detection range was 2–100 μg/ml (r²>0.999). Good repeatability of injection and relative migration times were obtained.     

Nucleoside transport in cultured mammalian cells multiple forms with different sensitivity to inhibition by nitrobenzylthioinosine or hypoxanthine

The zero-trans influx of 500 μM uridine by CHO, P388, L1210 and L929 cells was inhibited by nitrobenzylthioinosine (NBTI) in a biphasic manner; 60–70% of total uridine influx by CHO cells and about 90% of that in P388, L1210 and L929 cells was inhibited by nmolar concentrations of NBTI (ID₅₀ = 3?10 nM) and is designated NBTI-sensitive transport. The residual transport activity, designated NBTI-resistant transport, was inhibited by NBTI only at concentrations above 1 μM (ID₅₀ = 10?50 μM). S49 cells exhibited only NBTI-sensitive uridine transport, whereas Novikoff cells exhibited only NBTI-resistant uridine transport. In all instances NBTI-sensitive transport correlated with the presence of between 7·10⁴ and 7·10⁵ high-affinity NBTI binding sites/cell (K_d = 0.3?1 nM). Novikoff cells lacked such sites. The two types of nucleoside transport, NBTI-resistant and NBTI-sensitive, were indistinguishable in substrate affinity, temperature dependence, substrate specificity, inhibition by structurally unrelated substances, such as dipyridamole or papaverine, and inhibition by sulfhydryl reagents or hypoxanthine. We suggest, therefore, that a single nucleoside transporter can exist in an NBTI-sensitive and an NBTI-resistant form depending on its disposition in the plasma membrane. The sensitive form expresses a high-affinity NBTI binding site(s) which is probably made up of the substrate binding site plus a hydrophobic region which interacts with the lipophilic nitrobenzyl group of NBTI. The latter site seems to be unavailable in NBTI-resistant transporters. The proportion of NBTI-resistant and sensitive uridine transport was constant during proportion of NBTI-resistant and sensitive uridine transport was constant during progression of P388 cells through the cell cycle and independent of the growth stage of the cells in culture. There were additional differences in uridine transport between cell lines which, however, did not correlate with NBTI sensitivity and might be related to the species origin of the cells. Uridine transport in Novikoff cells was more sensitive to inhibition by dipyridamole and papaverine than that in all other cell lines tested, whereas uridine transport in CHO cells was the most sensitive to inactivation by sulfhydryl reagents.     

A new ginsenosidase from Aspergillus strain hydrolyzing 20-O-multi-glycoside of PPD ginsenoside

A ginsenosidase specifically hydrolyzing multi-20-O-glycosides of protopanaxadiol type ginsenosides such as ginsenoside Rb₁, Rb₃, Rb₂ and Rc, named ginsenosidase type II, was isolated and purified from Aspergillus sp.g48p strain. The molecular weight of the enzyme was 60 kDa. Ginsenosidase type II was demonstrated to hydrolyze multi-20-O-glycoside of protopanaxadiol type ginsenoside Rb₁, Rb₃, Rb₂ and Rc; i.e. the ginsenosidase type II hydrolyzes 20-O-β-glucoside of the ginsenoside Rb₁, 20-O-β-xyloside of ginsenoside Rb₃, 20-O-α-arabinoside(p) of ginsenoside Rb₂ and α-arabinoside(f) of ginsenoside Rc to produce mainly ginsenoside Rd, and small amount of Rg₃. However, it did not hydrolyze 3-O-β-glucosides of ginsenoside Rb₁, Rb₃, Rb₂ and Rc which was different with the ginsenosidase type I previously reported, either did not hydrolyze the glycosides of protopanaxatriol type ginsenoside such as ginsenoside Re, Rf and Rg₁, showing significant difference from all previously described glycosidases.     

New Specific α-Glucosidase Inhibitor Flavonoid from Thymelaea tartonraira Leaves: Structure Elucidation,Biological and Molecular Docking Studies

The phytochemical investigation of Thymelaea tartonraira leaves led to the isolation and characterization of six compounds, including one new flavonoid glycoside identified as hypolaetin 8-O-β-D-galactopyranoside ( 4 ) along with five known compounds, daphnoretin ( 1 ), triumbelletin ( 2 ), genkwanin ( 3 ), tiliroside ( 5 ) and yuankanin ( 6 ). Their structures were established based on spectroscopic methods, such as UV, IR, NMR, and HR-ESI-MS. Triumbelletin ( 2 ) and tiliroside ( 5 ) were isolated for the first time from T. tartonraira leaves. The antioxidant property of all isolated compounds was tested based on DPPH, FRAP and total antioxidant capacity assays. Compound 4 displayed an antioxidant potency more interesting than vitamin C with an IC₅₀=15.00±0.50 μg/ml, followed by compound 5 . Furthermore, the both compounds 4 and 5 were tested for their α-amylase inhibitory activity in-vitro. Compound 4 displayed higher potency to inhibit α-amylase, with an IC₅₀=46.49±2.32 μg/ml, than compound 5 , with an IC₅₀=184.2±9.2 μg/ml, while the reference compound acarbose presented the highest potency to inhibit α-amylase with an IC₅₀=0.44±0.022 μg/ml. Compound 4 displayed a strong inhibitory ability of α-glucosidase activity approximately twice more than the reference compound, acarbose, with IC₅₀ values of 60.00±3.00 and 125.00±6.25 μg/ml, respectively. Thus, compound 4 exhibited a specific inhibitory activity for α-glucosidase. The molecular docking studies have supported our findings and suggested that compound 4 has been involved in various binding interactions within the active site of both enzymes α-amylase and α-glucosidase.     

Morroniside cinnamic acid conjugate as an anti-inflammatory agent

A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell–cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC₅₀ = 49.3 μM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC₅₀ = 88.2 μM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-α-induced E-selectin expression.