Activity-guided investigation of Carissa carandas (L.) roots for anti-inflammatory constituents

The present study was structured to investigate the anti-inflammatory potential of the extracts, fractions and compounds isolated from Carissa carandas (L.) roots. Bioassay guided fractionation of methanol extract based on inhibitory potential towards proinflammatory mediators (TNF-α, IL-1β and nitric oxide (NO)) led to the identification of stigmasterol (1), lupeol (2), oleanolic acid (3), carissone (4) and scopoletin (5) as potential anti-inflammatory agents. Carissone (4) (IC₅₀ = 20.1 ± 2.69 μg/mL) and scopoletin (5) (IC₅₀ = 24.6 ± 1.36 μg/mL) exhibited significant inhibition of NO production comparable to specific NO inhibitor (L-NAME; IC₅₀ = 19.82 ± 1.64 μg/mL) without affecting the cell viability. Also, 4 and 5 at a concentration of 30 μM were found to inhibit 41.88–53.44% of TNF-α and IL-1β. To the best of our knowledge, this is the first report displaying the anti-inflammatory effects of C. carandas (L.) roots, partially mediated by inhibition of TNF-α, IL-1β and NO.     

Antioxidant,antimicrobial and urease inhibiting activities of methanolic extracts from Cyphostemma digitatum stem and roots

Cyphostemma digitatum stem and roots extracts were investigated for antioxidant, antimicrobial, urease inhibition potential and phytochemical analysis. Phytochemical screening of the roots and stem extract revealed the presence of secondary metabolites including flavonoids, alkaloids, coumarins, saponins, terpenoids, tannins, carbohydrates/reducing sugars and phenolic compounds. The methanolic extracts of the roots displayed highest antioxidant activity (93.518%) against DPPH while the crude methanolic extract of the stem showed highest antioxidant activity (66.163%) at 100 μg/mL concentration. The methanolic extracts of both stem and roots were moderately active or even found to be less active against the selected bacterial and fungal strains (Tables S2 and S3). The roots extract (methanol) showed significant urease enzyme inhibition activity (IC₅₀ = 41.2 ± 0.66; 0.2 mg/mL) while the stem extract was found moderately active (IC₅₀ = 401.1 ± 0.58; 0.2 mg/mL) against thiourea (IC₅₀ = 21.011; 0.2 mg/mL).     

Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf

The crude extracts of tubers of Aconitum spicatum (Bruhl) Stapf were investigated for in vitro antileishmanial activity against Leishmania major. The dichloromethane extract at pH 2.5 showed antileishmanial activity with IC₅₀ value of 27.10 ± 0.0 μg/mL. Chromatographic purification of the dichloromethane extract led to isolation of three C-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). Compounds 3 and 2 showed antileishmanial activity with IC₅₀ = 36.10 ± 3.4 and 56.30 ± 2.1 μg/mL, respectively. Compound 1 was less effective (IC₅₀ > 100 μg/mL). The cytotoxicity of compounds 1, 2 and 3 studied against MCF7, HeLa and PC3 cancer cell lines and 3T3 normal fibroblast cell line did not show cytotoxicity at 30 μM.     

Polyphenolic profiling of Ipomoea carnea Jacq. by HPLC-DAD and its implications in oxidative stress and cancer

Ipomoea carnea Jacq. is an important folklore medicinal plant, assessed for its underexplored biological potential. Antioxidant, cytotoxic, antiproliferative and polyphenolic profile of whole plant was evaluated using various techniques. Maximum extract recovery (29% w/w), phenolic [13.54 ± 0.27 μg GAE/mg dry weight (DW)] and flavonoid (2.11 ± 0.10 μg QE /mg DW) content were recorded in methanol-distilled water (1:1) flower extract. HPLC-DAD analysis quantified substantial amount of six different polyphenols ranging from 0.081 to 37.95 μg/mg extract. Maximum total antioxidant and reducing potential were documented in methanol-distilled water and acetone-distilled water flower extracts (42.62 ± 0.47 and 24.38 ± 0.39 μg AAE/mg DW) respectively. Ethanol-chloroform root extract manifested highest free radical scavenging (IC₅₀ of 61.22 μg/mL) while 94.64% of the extracts showed cytotoxicity against brine shrimps. Ethanol leaf extract exhibited remarkable activity against THP-1 cell line (IC₅₀ = 8 ± 0.05 μg/mL) and protein kinases (31 mm phenotype bald zone).     

Chemical constituents of essential oil of endemic Rhanterium suaveolens Desf. growing in Algerian Sahara with antibiofilm,antioxidant and anticholinesterase activities

Twenty compounds were detected in the essential oil of Rhanterium suaveolens representing 98.01% of the total oil content. Perillaldehyde (45.79%), caryophyllene oxide (24.82%) and β-cadinol (5.61%) were identified as the main constituents. In β-carotene–linoleic acid assay, both the oil and the methanol extract exhibited good lipid peroxidation inhibition activity, with IC₅₀ values of 17.97 ± 5.40 and 11.55 ± 3.39 μg/mL, respectively. In DPPH and CUPRAC assays, however, the methanol extract exhibited a good antioxidant activity. The highest antibiofilm activity has been found 50.30% against Staphylococcus epidermidis (MU 30) at 20 μg/mL for essential oil and 58.34% against Micrococcus luteus (NRRL B-4375) at 25 mg/mL concentration for methanol extract. The in vitro anticholinesterase activity of methanol extract showed a moderate acetylcholinesterase inhibitory (IC₅₀ = 168.76 ± 0.62 μg/mL) and good butyrylcholinesterase inhibitory (IC₅₀ = 54.79 ± 1.89 μg/mL) activities. The essential oil was inactive against both enzymes.     

Urease inhibitory profile of extracts and chemical constituents of Pistacia atlantica ssp. cabulica Stocks

The current study was designed to evaluate the urease inhibitory profile of extract and fractions of Pistacia atlantica ssp. cabulica Stocks followed by bioactivity-guided isolated compounds. The crude extract was found significantly active with urease inhibitor (95.40% at 0.2 mg/mL) with IC₅₀ values of 32.0 ± 0.28 μg/mL. Upon fractionation, ethyl acetate fraction displayed 100% urease inhibition with IC₅₀ values of 19.9 ± 0.51 μg/mL at 0.2 mg/mL. However, n-hexane and chloroform fractions exhibited insignificant urease inhibition. Similarly, the isolated compound, transilitin (1) and dihydro luteolin (2) demonstrated marked urease attenuation with 95 and 98% respectively, at 0.15 mg/mL. Both the isolated compounds showed marked potency with IC₅₀ values of 8.54 ± 0.54 and 9.58 ± 2.22 μg/mL, respectively. In short, both the extract and fractions and isolated compounds showed marked urease inhibition and thus a useful natural source of urease inhibition.     

Antioxidant,cholinesterase inhibition activities and essential oil analysis of Nelumbo nucifera seeds

Nelumbo nucifera seeds’ essential oil (EO), crude extract and subsequent fractions were evaluated for their DPPH, ABTS and superoxide anion-free radical scavenging and cholinesterase inhibitory activities. The ethyl acetate fraction and EO showed outstanding antioxidant activities with IC₅₀ values of 191, 450 μg/mL (DPPH), 123, 221 μg/mL (ABTS) and 69, 370 μg/mL (superoxide anion). The ethyl acetate fraction and EO also caused significant inhibition of acetylcholinesterase and butyrylcholinesterase with IC₅₀ values of 70 ± 0.6, 64 ± 0.8 and 75 ± 0.3, 58 ± 0.2, in dose-dependent manner. The first ever gas chromatography–mass spectrometry analysis of the EO obtained from N. nucifera seeds resulted in identification of 19 constituents, mainly comprised of oxygenated sesquiterpenes responsible for their promising bioactivity. The crude and fractions revealed the presence of saponins, flavonoids, steroids, alkaloids, terpenoids and cardiac glycosides in phytochemical investigation.     

A new butenolide cinnamate and other biological active chemical constituents from Polygonum glabrum

Phytochemical investigation of the methanol extract of the aerial parts of Polygonum glabrum afforded one new natural product ( ? )-2-methoxy-2-butenolide-3-cinnamate (1) along with six known compounds, β-hydroxyfriedalanol (2), 3-hydroxy-5-methoxystilbene (3), ( ? ) pinocembrin (4), sitosterol-(6′-O-palmitoyl)-3-O-β-d-glucopyranoside (5), ( ? ) pinocembrin-5-methyl ether (6) and sitosterol-3-O-β-d-glucopyranoside (7). Compound 1 showed promising in vitro anti-HIV-1 activity against primary isolates HIV-1_UG070 (X4, subtype D) and HIV-1_VB59 (R5, subtype C) assayed using TZM-bl cell line with IC₅₀ in the range of 15.68–22.43 μg/mL. The extract showed TI in the range of 19.19–27.37 with IC₅₀ in the range of 10.90–15.55 μg/mL. Compounds 1, 3 and 4 exhibited in vitro anti-mycobacterium activity against Mycobacterium tuberculosis H37Ra with IC₅₀ values of 1.43, 3.33 and 1.11 μg/mL in dormant phase and 2.27, 3.33 and 1.21 μg/mL in active phase, respectively. Compound 4 was found to be the most active antiproliferative with IC₅₀ values of 1.88–11.00 μg/mL against THP-1, A549, Panc-1, HeLa and MCF7 cell lines.     

GC-MS analysis of metabolites from soxhlet extraction,ultrasound-assisted extraction and supercritical fluid extraction of Salacca zalacca flesh and its alpha-glucosidase inhibitory activity

Abstract

Different extraction processes were employed to extract bioactive metabolites from Salacca zalacca flesh by a range of aqueous and organic solvents. The highest extraction yield was obtained by 50% ethanol extract of SE (73.18?±?4.35%), whereas SFE_1 showed the lowest yield (0.42?±?0.08%). All extracts were evaluated for in vitro α-glucosidase inhibitory activity, measured by their IC₅₀ values in comparison to that of quercetin, the positive control (IC₅₀ = 2.7?±?0.7?μg/mL). The lowest α-glucosidase inhibitory activity was indicated by water extract of SE (IC₅₀ = 724.3?±?42.9?μg/mL) and the highest activity was demonstrated by 60% ethanol extract by UAE (IC₅₀ = 16.2?±?2.4?μg/mL). All extracts were analysed by GC-MS and identified metabolites like carbohydrates, fatty acids, organic acids, phenolic acids, sterols and alkane-based compounds etcetera that may possess the potential as α-glucosidase inhibitor and may attribute to the α-glucosidase inhibitory activity.     

Anti-hydroxyl radical activity,redox potential and anti-AChE activity of Amanita strobiliformis polysaccharide extract

This study outlines antioxidant and anti-AChE activities of the polysaccharide (PSH) extract from the mushroom species Amanita strobiliformis. Both the presence of α and ß glucans within the aforementioned extract was recorded. PSH extract displayed a profound scavenging activity of OH radicals (IC₅₀ value, 11.86 ± 0.59 μg/mL) and high potential for reduction of Fe³⁺ ions (174.11 ± 8.70 mg eq. AA/g d.w.) being almost 48- and 5-fold more effective than mannitol and butylated hydroxytoluene used as a positive control, respectively. Compared with galanthamine (0.001 μg), the same extract exhibited a moderate anti-AChE activity (10 μg) in solid. Since purified PSH extract exhibited higher bioactivity (IC₅₀ value 7.27 ± 0.31 μg/mL, 197.68 ± 9.47 mg eq. AA/g d.w. and 0.1 μg, respectively), it can be predominantly ascribed to the polysaccharide compounds. A. strobiliformis PSH extract may be considered as a promising resource of potent bioactive polysaccharides of natural origin successfully addressing both oxidative stress and lack of acetylcholine.     

A contribution to pharmaceutical biology of freshwater sponges

In vitro anti-tumour and anti-radical activities of the acetone extract of the freshwater sponge Ochridaspongia rotunda were the subject of this study. The extract was found to be highly cytotoxic to human lung tumour cell line A-549 reaching IC₅₀ value of 5.01 ± 0.21 μg/mL. Indeed, it displayed only 2-fold less anti-tumour activity than doxorubicin (IC₅₀ value 2.42 ± 0.13 μg/mL) used as a positive control. The same extract was also found to be almost 37-fold more selective against A-549 vs. MRC-5 (normal) lung cells, in difference to weak selectivity of doxorubicin (less than 3-fold). Its profound anti-DPPH radical activity comparable to that of quercetin (IC₅₀ values 3.68 ± 0.19 and 3.14 ± 0.09 μg/mL, respectively) coupled with no signs of genotoxicity in the comet assay (MRC-5 cell line, vs. doxorubicin) has actually implicated the importance of this animal bioresource in searching for pharmaceutically useful bioactive compounds of natural origin.     

Chemical characterisation of the constituents of Eugenia protenta McVaugh and leishmanicidal activity of dimethylxanthoxylin

The chemical study of Eugenia protenta McVaugh extracts performed by classical and high-performance liquid chromatography techniques and spectral methods has led to the identification of known triterpenoids, flavonoids and an acetophenone derivative (dimethylxanthoxylin). The effect of dimethylxanthoxylin on Leishmania (Leishmania) amazonensis was evaluated against the promastigotes forms after 96 h of treatment. Dimethylxanthoxylin reduced 57 and 59% of the promastigotes growth when treated with 50 and 100 μg/mL solutions, respectively (IC₅₀ 117.35 μg/mL or 52.3 μM). Cytotoxicity experiments using MTT assays showed that this substance did not promote cell death after 24 h of treatment. Dimethylxanthoxylin was active on the promastigotes and could be a promising agent for treating leishmaniasis.     

Cytotoxicity of syringin and 4-methoxycinnamyl alcohol isolated from Foeniculum vulgare on selected human cell lines

This study was carried out to determine the cytotoxic effect of seven plant extracts and the isolated compounds – syringin and 4-methoxycinnamyl alcohol – on cancerous and non-cancerous cells. The ethanol extract of Foeniculum vulgare was found to exhibit the most significant toxicity with an IC₅₀ value of 19.97 μg/mL on HeLa cells. Bioassay-guided fractionation led to the isolation of two compounds, syringin (1) and 4-methoxycinnamyl alcohol (2). Both compounds showed toxicity against MCF-7, HeLa and DU145 cancer cell line. The results showed that compound 2 showed high toxicity against all the cancer cell lines with IC₅₀ values of 14.24, 7.82 and 22.10 μg/mL, respectively. 4-Methoxycinnamyl alcohol also showed no apoptotic effect in cell cycle analysis after 48 h at a concentration of 10 μg/mL. However, DNA fragmentation study revealed that necrosis took place at a concentration of 10 μg/mL after 48 h exposure.     

Structure activity relationship of bergenin,p-hydroxybenzoyl bergenin, 11-O-galloylbergenin as potent antioxidant and urease inhibitor isolated from Bergenia ligulata

Ethanol extract of the aerial parts of Bergenia ligulata was subjected to solvent–solvent separation followed by various chromatographic techniques that lead to isolation of bergenine (1), p-hydroxybenzoyl bergenin (2), 11-O-galloylbergenin (3) and methyl gallate (4) as major constituents. Ethyl acetate fraction showed a dose-dependent urease inhibitory pattern with IC₅₀ value of 54μg/mL. Structures of compounds 1 and 3 were established by XRD and 2, 4 by NMR. All these compounds were subjected to DPPH scavenging activity, reducing power assay and urease inhibitory activity. The EC₅₀ 7.45 ± 0.2 μg/mL and 5.39 ± 0.28 μg/mL values in terms of antioxidant and reducing power, respectively, were less for 3. Compounds 1–3 showed moderate to significant urease inhibitory potential with IC₅₀ 57.1 ± 0.7, IC₅₀ 48.4 ± 0.3 and 38.6 ± 1.5. Antioxidant activities and urease inhibitory potential were investigated and compound 3 was found to be the most active.     

Chemical composition and in vitro antibacterial and antiproliferative activities of the essential oil from the leaves of Psidium myrtoides O. Berg (Myrtaceae)

In this study, the chemical composition and antibacterial and antiproliferative potential of the essential oil obtained from fresh leaves of Psidium myrtoides (PM-EO) against oral pathogens and human tumour cell lines were investigated for the first time. GC-FID and GC-MS analyses showed that trans-β-caryophyllene (30.9%), α-humulene (15.9%), α-copaene (7.8%), caryophyllene oxide (7.3%) and α-bisabolol (5.3%) are the major constituents of PM-EO. The antibacterial activity of PM-EO against a panel of oral pathogens was investigated in terms of their minimal inhibitory concentrations (MIC) using the broth microdilution method. PM-EO displayed moderate activity against Streptococcus mitis (MIC = 100 μg/mL), S. sanguinis (MIC = 100 μg/mL), S. sobrinus (MIC = 250 μg/mL), and S. salivarius (MIC = 250 μg/mL), and strong activity against S. mutans (MIC = 62.5 μg/mL). The antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumour cell lines (MCF-7, HeLa, and M059 J) was performed using the XTT assay. PM-EO showed 50% inhibition of normal cell growth at 359.8 ± 6.3 μg/mL. Antiproliferative activity was observed against human tumour cell lines, with IC₅₀ values significantly lower than that obtained for the normal cell line, demonstrating IC₅₀ values for MCF-7 cells (254.5 ± 1.6 μg/mL), HeLa cells (324.2 ± 41.4 μg/mL) and M059 J cells (289.3 ± 10.9 μg/mL). Therefore, the cytotoxicity of PM-EO had little influence on the antibacterial effect, since it showed antibacterial activity at lower concentrations. Our results suggest that PM-EO is a promising source of new antibacterial and antitumour agents.     

α-Glucosidase inhibitory activity of marine sponges collected in Mauritius waters

This report describes the use of α-glucosidase to evaluate the anti-diabetic potential of extracts from marine sponges collected in the Mauritius waters. Initial screening at 1.0 mg/mL of 141 extracts obtained from 47 sponge species revealed 10 extracts with inhibitory activity greater than 85%. Seven of the 10 extracts were further tested at 0.1 and 0.01 mg/mL and only the methanol extract of two sponges namely Acanthostylotella sp. (ASSM) and Echinodictyum pykei (EPM) showed inhibition activity greater than 60% at 0.1 mg/mL with an IC₅₀ value of 0.16 ± 0.02 and 0.04 ± 0.01 mg/mL, respectively, while being inactive at 0.01 mg/mL.     

Isolation and structural modifications of ananixanthone from Calophyllum teysmannii and their cytotoxic activities

Two naturally occurring xanthones, ananixanthone (1) and β-mangostin (2), were isolated using column chromatographic method from the n-hexane and methanol extracts of Calophyllum teysmannii, respectively. The major constituent, ananixanthone (1), was subjected to structural modifications via acetylation, methylation and benzylation yielding four new xanthone derivatives, ananixanthone monoacetate (3), ananixanthone diacetate (4), 5-methoxyananixanthone (5) and 5-O-benzylananixanthone (6). Compound 1 together with its four new derivatives were subjected to MTT assay against three cancer cell lines; SNU-1, K562 and LS174T. The results indicated that the parent compound has greater cytotoxicity capabilities against SNU-1 and K562 cell lines with IC₅₀ values of 8.97 ± 0.11 and 2.96 ± 0.06 μg/mL, respectively. Compound 5 on the other hand exhibited better cytotoxicity against LS174T cell line with an IC₅₀ value of 5.76 ± 1.07 μg/mL.     

Biological activity and LC-MS/MS profiling of extracts from the Australian medicinal plant Acacia ligulata (Fabaceae)

Acacia ligulata A.Cunn. ex Benth. (Fabaceae: Mimosoideae) is a native Australian plant used traditionally by Australian Aboriginal groups. This study was undertaken to investigate the bioactivity of A. ligulata extracts and to evaluate their chemical composition. Potential antibacterial, cytotoxic and enzyme inhibitory effects relevant to traditional medicinal and food uses of the species were examined and LC-MS/MS was performed to investigate the chemical composition. Antibacterial activity was observed for bark and leaf extracts with an MIC for the bark extract of 62.5 μg/mL against Streptococcus pyogenes. Pod extracts showed cytotoxic effects against cancer cells, with the highest activity against melanoma SK-MEL28 cells with IC₅₀ values between 40.8 and 80.6 μg/mL. Further, the leaf and pod extracts also inhibited α-amylase EC-3.2.1.1 and α-glucosidase EC-3.2.1.20 with IC₅₀ values between 9.7–34.8 and 12.6–64.3 μg/mL, respectively. The LC-MS/MS profiling indicated that several different saponins were present in the active extracts.     

New α-glucosidase inhibiting anthracenone from the barks of Harungana madagascariensis Lam

Two new 10-hydroxy-9(10H)-anthracenone, madagascenone A (1) and B (2), were isolated from the barks of Harungana madagascariensis Lam. The structures of the compounds were determined using 1D- and 2D-NMR and mass spectroscopic techniques. Both of the compounds showed an in vitro α-glucosidase inhibition with IC₅₀ = 69.9 ± 4.21 and 122.3 ± 1.13 μM, respectively, more potent than the standard acarbose (IC₅₀ = 840 ± 1.23 μM).     

New chemical constituents from the Piper betle Linn. (Piperaceae)

The phytochemical investigation of chloroform extract from Piper betle var. haldia, Piperaceae, leaves has resulted in the isolation of two new chemical constituents which were identified as 1-n-dodecanyloxy resorcinol (H1) and desmethylenesqualenyl deoxy-cepharadione-A (H4), on the basis of spectroscopic data 1D NMR (¹H and ¹³C) and 2D NMR (¹H-¹H COSY and HMBC) as well as ESI-MS, FT-IR and HR-ESI-MS analyses. Compounds H1 and H4 showed excellent antioxidant DPPH free radical scavenging activity with IC₅₀ values of 7.14 μg/mL and 8.08 μg/mL compared to ascorbic acid as a standard antioxidant drug with IC₅₀ value of 2.52 μg/mL, respectively. Evaluation of cytotoxic activity against human hepatoma cell line (PLC-PRF-5) showed moderate effect with the GI₅₀ values of 35.12 μg/mL for H1, 31.01 μg/mL for H4, compared to Doxorubicin^® as a standard cytotoxic drug with GI₅₀ value of 18.80 μg/mL.