Anti-inflammatory,cyclooxygenase (COX)-2, COX-1 inhibitory and antioxidant effects of Dysophylla stellata Benth.

The n-hexane and ethyl acetate extracts of whole plants of Dysophylla stellata significantly inhibited edema when applied topically at doses of 0.5 and 1 mg/ear in TPA-induced ear edema assay in mice. Further, both the extracts were evaluated for COX-1 and COX-2 inhibitory activities and showed 85.42 and 57.38%; and 71.79 and 89.27% inhibition at 50 µg/ml, respectively. Chromones (1 and 2) present in these extracts could be responsible for their COX-1 and COX-2 inhibitory and anti-inflammatory activities. The ethyl acetate extract showed antioxidant activity in DPPH and ABTS radical scavenging assay where as n-hexane extract found to be inactive.     

Inhibition of viral adsorption and penetration by an aqueous extract from Rhododendron ferrugineum L. as antiviral principle against herpes simplex virus type-1

The polyphenol-enriched aqueous extract RF from the aerial parts of Rhododendron ferrugineum exhibited strong antiviral activity against herpes simplex virus type-1 while adenovirus 3 was not affected. RF exhibited an IC₅₀ of 7.4 μg/mL and a selectivity index of 64 when added to the virus inoculum prior to infection. RF abolished virus entry into the host cell by blocking attachment to the cell surface. When added after attachment at a concentration of > 25 μg/mL, RF inhibited also penetration of HSV-1 into the host cell. RF directly interacts with viral envelope proteins as demonstrated for the viral glycoprotein gD.     

Cytotoxic and anti-inflammatory ent-kaurane diterpenoids from Isodon wikstroemioides

Seven new ent-kaurane diterpenoids, isowikstroemins A–G (1–7), were isolated from EtOAc extracts of the aerial parts of Isodon wikstroemioides. Their structures were elucidated by extensive spectroscopic analysis. The isolates were evaluated for their cytotoxicity against five human tumor cell lines, and compounds 1–4 exhibited significant activity with IC₅₀ values ranging from 0.9 to 7.0 μM. In addition, compounds 1, 2, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages.     

Antiinflammatory activity of Sambucus ebulus hexane extracts

Hexane extracts of aerial parts (flowered browes), leaves and roots of Sambucus ebulus were investigated for their antiinflammatory activity in rats. Aerial parts and roots extracts produced statistically significant and dose dependent inhibition of edema induced by carrageenan at all doses when compared to the control groups. On the contrary, hexane extract of leaves did not show any activity up to 600 mg/kg i.p. The highest activity was showed in the aerial parts and roots that at 600 mg/kg i.p. inhibited inflammation by ca. 80% (78% for diclofenac at 100 mg /kg i.p.). No extracts exhibit toxicity when injected up to 2 g/ kg intraperitoneally in mice.     

Two new benzofuran derivatives with anti-inflammatory activity from Liriope spicata var. prolifera

Two new benzofuran derivatives, 2-(4′-hydroxybenzyl)-5,6-methylenedioxy-benzofuran () and 2-(4′-hydroxybenzoyl)-5,6-methylenedioxy-benzofuran (), along with 8 known compounds were isolated from 60% EtOH extract of the fibrous roots of Liriope spicata var. prolifera. Their structures were elucidated on the basis of extensive spectroscopic analysis. In an in vitro bioactive assay, the two new benzofuran derivatives showed anti-inflammatory activity. Compounds 1 and 2 exhibited significant inhibitory activity against neutrophil respiratory burst stimulated by phorbol 12-myristate 13-acetate (PMA) with IC₅₀ value of 4.15 ± 0.07 and 5.96 ± 0.37 μM, respectively.     

Determination of chemical profile, antioxidant, DNA damage protection and antiamoebic activities of Teucrium polium and Stachys iberica

This work deals with the evaluation of in vitro antioxidant, DNA preventing and antiamoebic activities of the water extracts of Teucrium polium and Stachys iberica. In all systems, T. polium extract exhibited excellent activity potential than that of S. iberica. The amount of total phenolics and flavonoids were high in this extract. In the presence of 40 mg/ml T. polium extract, a significant protection was observed for native super coiled DNA of pBR322 plasmid DNA. In the presence of 32 mg/ml of T. polium extract, no trophozoite was after the 24th hour.     

Aporphine alkaloids,clerodane diterpenes,and other constituents from Tinospora cordifolia

Phytochemical investigation of the methanol extract of Tinospora cordifolia aerial parts led to the isolation of four new and seven known compounds. The structures of two new aporphine alkaloids, N-formylasimilobine 2-O-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranoside (tinoscorside A, 1) and N-acetylasimilobine 2-O-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranoside (tinoscorside B, 2), a new clerodane diterpene, tinoscorside C (3), and a new phenylpropanoid, sinapyl 4-O-β-d-apiofuranosyl-(1 → 6)-O-β-d-glucopyranoside (tinoscorside D, 6) were determined by extensive spectroscopic methods including FTICR-MS and 1D and 2D NMR.     

Puqienine E: An angiotensin converting enzyme inhibitory steroidal alkaloid from Fritillaria puqiensis

Eight steroidal alkaloids, puqienine A, puqienine B, puqienine C, puqienine D, puqienine E, puqietinone, puqiedine and peimisine were isolated from Fritillaria puqiensis G. D. Yu et. G. Y. Chen, and their anti-hypertensive effect were assessed in vitro based on the inhibition of the purified angiotensin converting enzyme (ACE) using high-performance liquid chromatography assay. The results showed that puqienine E, puqienine B and puqienine A exhibited better inhibitory activity against ACE than others, with inhibition ratios of 70.2 ± 0.5%, 24.7 ± 0.5% and 20.4 ± 2.8%, respectively at the concentration of 200 μM. The 50% inhibiting concentration of puqienine E was determined to be 68 µM.     

Cytochrome P450 1 enzyme inhibition and anticancer potential of chromene amides from Amyris plumieri

Cytochrome P450 (CYP) enzyme inhibitory properties of six chromenylated amide compounds (CAs) from Amyris plumieri are described. Inhibition of CYP microsomes (CYP1A1, CYP1A2, CYP1B1, CYP2D6, CYP3A4 and CYP2C19) was monitored using a fluorescent assay. Potent inhibition was found against CYP1A1 with IC₅₀ and K_i for CA1 (acetamide), being the lowest at 1.547 ± 1.0 μM and 0.37 μM respectively, displaying non-competitive kinetics. The selectivity for CYP1A1 was increased in CA3 (butanamide), which also exhibited cytotoxicity against breast cancer cells, MCF7 with an IC₅₀ of 47.46 ± 1.62 μM. Structure-activity relationship studies provide insight at a molecular level for CAs with implications in chemoprevention and chemotherapy.     

Prenylated phloroglucinol derivatives from Hypericum sampsonii

Six new acylphloroglucinol derivatives, sampsonols A-F (1–6), were isolated from the petroleum ether extract of the aerial parts of Hypericum sampsonii. The structures and relative configurations of sampsonols A-F were elucidated by extensive spectroscopic analyses. All these compounds were tested for their in vitro cytotoxic and anti-inflammatory activities. Sampsonols A and B (1 and 2) showed significant cytotoxicity against four human tumor cell lines with IC₅₀ values in the range of 13–28 μM, whereas sampsonols C and F (3 and 6) showed potent inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages with IC₅₀ values of 27.3 and 29.3 μM, respectively.     

Antinociceptive and antiplasmodial activities of cassane furanoditerpenes from Caesalpinia volkensii H. root bark

The chloroform and ethyl acetate extract (100 mg/kg) of Caesalpinia volkensii H. exhibited significant (P ≤ 0.05) antinociceptive activities using hot plate and writhing tests in mice while the later showed antiplasmodial activity (IC₅₀ 0.23 ± 0.07 and 4.39 ± 2.49 μg/ml) against chloroquine sensitive (D6) and chloroquine-resistant (W2), respectively. Two new furanoditerpenes [rel. 1β,5α-dihydroxyvoucapane (1) and rel. 1β,6β-dihydroxyvoucapane; 19β-methyl ester (2)] together with seven known compounds [voucapane (3), voucapan-5-ol (4), deoxycaesaldekarin C (5), caesaldekarin C (6), 5-hydroxyvinhaticoic acid (7), triacontanyl-(E)-ferulate (8), triacontanyl-(E)-caffaete (9) and 30′-hydroxytriacontanyl-(E)-ferulate (10)] were isolated from the two extracts. The administration of 3, 4, 5 and 6 (100 mg/kg i.p) caused a significant (P ≤ 0.05) reduction in the number of writhing episodes induced by acetic acid and (P ≤ 0.01) increased pain latency threshold in hot-plate test compared to control. However, the pure compounds indicated relatively (P ≤ 0.05) low antiplasmodial activity. The phytochemical constituents from the root bark of C. volkensii had better analgesic properties than antimalarial properties, justifying the use of the plant root bark as a remedy for pain.     

Isolation and structural characterization of glycosides from an anti-angiogenic extract of Monnina obtusifolia H.B.K.

Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is of physiological and pathological importance. Substantial data over the last decade has implicated uncontrolled angiogenesis with various pathological states. Vascular endothelial growth factors (VEGFs) play a critical role in its regulation, and have become one of the most interesting anti-angiogenesis targets. We have investigated the anti-angiogenic potential of plant extracts in a preliminary ELISA screening. The n-BuOH extract obtained from the leaves of Monnina obtusifolia (Polygalaceae) demonstrated an inhibition of VEGF-A or Placental Growth Factor interaction with Flt-1 (VEGF receptor 1), with an inhibition over 50% in particular for VEGF-A/Flt-1 interaction at a concentration of 500 μg/mL. Successively fractionation of the bioactive n-BuOH extracts of M. obtusifolia aerial parts led to the isolation of six new compounds, 1-O-(4-hydroxy-2-methylene-butanoic acid)-6-O-β-d-(4-hydroxy-2-methylene-butanoyl)-glucopyranose (1), 1-O-(isopentenyl)-6-O-β-d-(4-hydroxy-2-methylene-butanoyl)-glucopyranose (2), 1-O-(4-hydroxy-2-methylene-butanoic acid)-6-O-β-d-(isovaleroyl)-glucopyranose (3), 1-O-(3-methylbut-3enyl)-6-O-β-d-(isovaleroyl)-glucopyranose (4), two new sucrose esters, 3,4-O-β-d-di-feruloyl-fructofuranosyl-6-O-α-d-(p-coumaroyl)-glucopyranoside (5), and 3,4-O-β-d-di-feruloyl-fructofuranosyl-6-O-α-d-(caffeoyl)-glucopyranoside (6), together with known flavonoids. Their structures were established on the basis of detailed spectral analysis. Since none of the isolated compounds showed a relevant inhibition of VEGFs, the biological activity observed for the butanolic extract might be due to the presence of a combination of compounds acting synergistically.     

Anticholinesterase activity of standardized extract of Illicium verum Hook. f. fruits

Illicium verum is a well known spice in traditional Indian system for its therapeutic potential. The present study was aimed to evaluate the acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory (BChE) activity of standardized extracts of I. verum and its oil. Present study confirmed that anethole contributed to the anticholinesterase activity of I. verum, with more specificity towards AChE. IC₅₀ for AChE and BChE inhibitory activity of anethole was 39.89 ± 0.32 μg/mL and 75.35 ± 1.47 μg/mL, whereas for the oil, 36.00 ± 0.44 μg/mL and 70.65 ± 0.96 μg/mL respectively. Therefore I. verum can be a good lead as anti-cholinesterase agent from natural resources.     

Intsia palembanica wood extracts and its isolated compounds as Propionibacterium acnes lipase inhibitor

Potential compounds from Intsia palembanica methanol extracts were isolated. Three isolated compounds as well as 7 reported compounds from Merbau were analyzed for their ability to inhibit the lipase activity of Propionibacterium acnes. Lipase was isolated from P. acnes and used as enzyme for activity analysis. The lipase activity test was performed using the 2,3-dimercapto-1-propanol tributyrate (BALB) method. The results showed that methanol extract and water fraction were active to inhibit lipase activity but n-hexane fraction and EtOAc fraction did not reach 50 % inhibition until 500 μg/ml. EtOAc fraction consisted of flavonoid, naringenin, robinetin, and (+)-epirobidanol accelerated the lipase activity. The other 7 compounds showed inhibitory activity of lipase in a concentration-dependent manner. In conclusion, fustin is the most active compound to inhibit the P. acnes lipase activity.     

New flavonol glycosides from Aconitum burnatii Gáyer and Aconitum variegatum L.

Six flavonol glycosides, compounds 1-3 from A. burnatii Gáyer and 4-6 from A. variegatum L., were obtained from their methanol extracts of aerial parts. The identified structures were quercetin 3-O-β-d-glucopyranoside-7-O-(6-E-p-coumaroyl)-β-d-glucopyranosyl-(1 → 3)-α-l-rhamnopyranoside (1), quercetin 3-O-β-d-glucopyranoside-7-O-β-d-glucopyranosyl-(1 → 3)-α-l-rhamnopyranoside (2), quercetin 3-O-β-d-glucopyranoside-7-O-(6-E-caffeoyl)-β-d-glucopyranosyl-(1 → 3)-α-l-rhamnopyranoside (3), kaempferol 3-O-β-d-galactopyranoside-7-O-α-l-arabinopyranoside (4), quercetin 3-O-β-d-glucopyranoside (5), and kaempferol 3-O-β-d-glucopyranoside (6). Compounds 1, 2 and 4 were isolated for the first time. The antioxidant potential of the methanol extracts and pure compounds was tested with different assays.     

Evaluation of analgesic, anti-inflammatory and hepatoprotective effects of lycorine from Sternbergia fisheriana (Herbert) Rupr

The present study reports the potential antinociceptive, anti-inflammatory and hepatoprotective activities of lycorine from Sternbergia fischeriana (Herbert) Rupr. (Amaryllidaceae). Lycorine was evaluated on mice by using acetic-acid induced writhing and tail-flick tests. Lycorine exhibited stronger inhibition than aspirin in acetic-acid induced abdominal stretching at 1.0 mg/kg dose. Lycorine also showed antinociceptive activity at 1.0 mg/kg dose in tail-flick test. The anti-inflammatory activity of lycorine was not found to be significant at dose of 0.5 mg/kg. However, at doses of 1.0 mg/kg and 1.5 mg/kg, i.p. showed a significant reduction with 53.45% and 36.42%, respectively in rat paw oedema induced by carrageenan against the reference anti-inflammatory drug indomethacin (3 mg/kg, i.p.) (95.70%). The ED₅₀ of lycorine was determined as 0.514 mg/kg. Hepatoprotective activity of lycorine on carbon tetrachloride (CCl₄) induced acute liver toxicity following biochemical parameters were also evaluated. Rats were treated with lycorine at doses of 1.0 mg/kg and 2.0 mg/kg, i.p. Results of biochemical tests were confirmed by histopathological examination. Lycorine exhibited significant hepatoprotective effect at dose of 2.0 mg/kg i.p. dose.     

Bioactive flavones and biflavones from Selaginella moellendorffii Hieron

Three new flavones named 5-carboxymethyl-4′,7-dihydroxyflavone (1), its ethyl ester (2) and butyl ester (3) were isolated from the herb Selaginella moellendorffii Hieron., together with ten known compounds. Their structures were elucidated on the basis of spectroscopic and chemical analysis. Selected compounds were evaluated for their anti-HBV and cytotoxic activity. Among them, compounds 2 and 3 displayed inhibitory activity in vitro on hepatitis B virus (HBV) surface antigen (HBsAg) secretion of the Hep G2.2.15 cell line with IC₅₀ values of 0.17 mg/ml and 0.46 mg/ml, and on HBV e antigen (HBeAg) secretion with IC₅₀ values of 0.42 mg/ml and 0.42 mg/ml, respectively. Compounds 7, 8, 10 and 12 exhibited selective cytotoxicity against the three human cancer cell lines tested.     

Pistagremic acid,a glucosidase inhibitor from Pistacia integerrima

Pistacia integerrima Stewart in traditionally used as folk remedy for various pathological conditions including diabetes. In order to identify the bioactive compound responsible for its folk use in diabetes, a phytochemical and biological study was conducted. Pistagremic acid (PA) was isolated from the dried galls extract of P. integerrima. Strong α-glucosidase inhibitory potential of PA was predicted using its molecular docking simulations against yeast α-glucosidase as a therapeutic target. Significant experimental α-glucosidase inhibitory activity of PA confirmed the computational predictions. PA showed potent enzyme inhibitory activity both against yeast (IC₅₀: 89.12 ± 0.12 μM) and rat intestinal (IC₅₀: 62.47 ± 0.09 μM) α-glucosidases. Interestingly, acarbose was found to be more than 12 times more potent an inhibitor against mammalian (rat intestinal) enzyme (having IC₅₀ value 62.47 ± 0.09 μM), as compared to the microbial (yeast) enzyme (with IC₅₀ value 780.21 μM). Molecular binding mode was explored via molecular docking simulations, which revealed hydrogen bonding interactions between PA and important amino acid residues (Asp60, Arg69 and Asp 70 (3.11 Å)), surrounding the catalytic site of the α-glucosidase. These interactions could be mainly responsible for their role in potent inhibitory activity of PA. PA has a strong potential to be further investigated as a new lead compound for better management of diabetes.     

Screening of Indonesian medicinal plants for inhibitor activity on nitric oxide production of RAW264.7 cells and antioxidant activity

Traditional Indonesian medicinal plants were screened for their inhibitory effects on the nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and for the antioxidant activity through the evaluation of free radical scavenging effect and reducing power. The results of screening indicated that 50 methanolic extracts inhibited (>50%) lipopolysaccharides (LPS)-induced NO release from RAW264.7 cells at 50 microg/ml, with 18 having greater than 100% inhibition. At 200 microg/ml, 61 methanol extracts exhibited inhibitory activity (>50%), with 45 showing greater than 100% inhibition. In addition, the free radical scavenging effects of 6 methanolic extracts were found to be more than 50% for extract concentration of 0.5 mug/ml. The results indicate that the extracts contain active compounds that inhibit NO release and scavenge free radical.     

Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale)

Ginger roots have been used to treat inflammation and have been reported to inhibit cyclooxygenase (COX). Ultrafiltration liquid chromatography mass spectrometry was used to screen a chloroform partition of a methanol extract of ginger roots for COX-2 ligands, and 10-gingerol, 12-gingerol, 8-shogaol, 10-shogaol, 6-gingerdione, 8-gingerdione, 10-gingerdione, 6-dehydro-10-gingerol, 6-paradol, and 8-paradol bound to the enzyme active site. Purified 10-gingerol, 8-shogaol and 10-shogaol inhibited COX-2 with IC₅₀ values of 32 μM, 17.5 μM and 7.5 μM, respectively. No inhibition of COX-1 was detected. Therefore, 10-gingerol, 8-shogaol and 10-shogaol inhibit COX-2 but not COX-1, which can explain, in part, the anti-inflammatory properties of ginger.