Anti-inflammatory abietane diterpenoids from the seeds of Podocarpus nagi

In searching for naturally occurring anti-inflammatory agents, three new abietane-type diterpenoids, named 16-hydroxylambertic acid (1), 7-oxo-18-hydroxyferruginol (2), and 5α,12-dihydroxy-6-oxa-abieta-8,11,13-trien-7-one (3), were isolated from the seeds of Podocarpus nagi, together with three known compounds. The structures of the new compounds were elucidated by extensive analysis of NMR and HR-ESIMS data. All the new compounds were tested for nitric oxide (NO) inhibitory activities on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Compound 1 significantly inhibited NO production with IC₅₀ value of 5.38 ± 0.17 μM, and suppressed inducible NO synthase (iNOS) expression in a dose-dependent manner, which were mediated through inhibiting the mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) activation.     

Anti-inflammatory components of Euphorbia humifusa Willd.

Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3–26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10–21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC₅₀ values as low as 18.05 ± 1.17, 18.64 ± 1.83, and 17.23 ± 0.84 μM, respectively. In addition, the effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compounds 3–6, 8, 18, 20–23, and 25–26 inhibited the production of both NO and TNF-α, with IC₅₀ values ranging from 11.1 ± 0.9 to 45.3 ± 1.6 μM and 14.4 ± 0.5 to 44.5 ± 1.2 μM, respectively.     

Novel phenolic and diterpenoid compounds isolated from the fruit spikes of Prunella vulgaris L. and their anti-inflammatory activities

Two novel phenolic compounds, prunellanate A (1) and prunellanate B (2), together with a diterpenoid compound, prunelladiterpenol A (3), were successfully isolated from the fruit spikes of Prunella vulgaris L. (Figure 1). Their structures were determined after extensive spectroscopic analyses including IR NMR, HR-ESI-MS empirical electronic circular dichroism (ECD), and X-ray diffraction. The biological activities of these new compounds on NO production in LPS (Lipopolysaccharide)-simulated RAW264.7 cells were evaluated. Compounds 1 and 3 showed significant anti-inflammatory activities revealing IC₅₀ values of 6.77 and 8.61 μM, respectively (aminoguanidine as positive control, IC₅₀ 20.33 ± 1.08 μM).     

C19-Diterpenoid alkaloids from Aconitum richardsonianum

Three new aconitine-type C₁₉-diterpenoid alkaloids, richardsonines A-C (1–3), were isolated from the roots of Aconitum richardsonianum Lauener, together with seventeen known compounds (4–20). Their structures were elucidated by extensive spectroscopic analysis, and the absolute stereochemistry of 1 was confirmed by X-ray crystallography. Compounds 2, 5, 8 and 9 were rare C₁₉-diterpenoid alkaloids bearing an OH group at C-16. Isolated compounds were evaluated for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated neuroinflammatory responses in BV-2 microglial cells. Compounds 3 and 7 showed weak antineuroinflammatory effects with inhibition rates of 35.32 ± 2.29% and 39.94 ± 2.50%, respectively, at a concentration of 100 µM.     

Chemical constituents from the fruit of Gardenia jasminoides and their inhibitory effects on nitric oxide production

Three new iridoid glycosides, 6″-O-trans-caffeoylgenipin gentiobioside (1), genipin 1-O-β-d-apiofuranosyl (1→6)-β-d-glucopyranoside (2), genipin 1-O-α-d-xylopyranosyl (1→6)-β-d-glucopyranoside (3), three new monocyclic monoterpenoids, jasminoside R (4), jasminoside S (5), jasminoside T (6), together with nine known iridoid glycosides (7–15) and three crocetin glycosides (16–18), were isolated from the fruit of Gardenia jasminoides. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Inhibitory effects of the isolated compounds on nitric oxide production in lipopolysaccaride-activated macrophages were evaluated. Compounds 8 and 18 showed strong inhibitory activity on NO production with IC₅₀ values of 11.14 ± 0.67 and 5.99 ± 0.54 μM, respectively.     

Anti-inflammatory norditerpenoids from the soft coral Sinularia maxima

Chemical investigation of the soft coral Sinularia maxima resulted in the isolation of seven norditerpenoids, including two new compounds, 12-hydroxy-scabrolide A (2) and 13-epi-scabrolide C (6). The structures of the isolated compounds were elucidated based on extensive spectroscopic evidence including Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and both one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR, respectively), in comparison with reported data. Compound 6 potently inhibited IL-12 and IL-6 production in LPS-stimulated bone marrow derived dendritic (BMDCs) with IC₅₀ values of 5.30 ± 0.21 and 13.12 ± 0.64 μM, respectively. Compound 1 exhibited moderate inhibitory activity against IL-12 and IL-6 production with IC₅₀ values of 23.52 ± 1.37 and 69.85 ± 4.11 μM, respectively.     

A new isoflavonol and other constituents from Cameroonian propolis and evaluation of their anti-inflammatory,antifungal and antioxidant potential

Propolis is rich in diverse bioactive compounds. Propolis samples were collected from three localities of Cameroon and used in the study. Column chromatography separation of propolis MeOH:DCM (50:50) extracts yielded a new isoflavonol, 2-hydroxy-8-prenylbiochanin A (1) alongside 2′,3′-dihydroxypropyltetraeicosanoate (2) and triacontyl p-coumarate (3) isolated from propolis for first time together with seven compounds: β-amyrine (4), oleanolic acid (5), β-amyrine acetate (6), lupeol (7), betulinic acid (8), lupeol acetate (9) and lupenone (10). These compounds were tested for their inhibitory effect on oxidative burst where intracellular reactive oxygen species (ROS) were produced from zymosan stimulated human whole blood phagocytes and on production of nitric oxide (NO) from lipopolysaccharide (LPS) stimulated J774.2 mouse macrophages. The cytotoxicity of these compounds was evaluated on NIH-3 T3 normal mouse fibroblast cells, antiradical potential on 2,2-diphenyl-1-picrylhydrazylhydrazyl (DPPH·) as well as their anti-yeast potential on four selected candida species. Compound 1 showed higher NO inhibition (IC₅₀ = 23.3 ± 0.3 µg/mL) than standard compound L-NMMA (IC₅₀ = 24.2 ± 0.8 µg/mL). Higher ROS inhibition was shown by compounds 6 (IC₅₀ = 4.3 ± 0.3 µg/mL) and 9 (IC₅₀ = 1.1 ± 0.1 µg/mL) than Ibuprofen (IC₅₀ = 11.2 ± 1.9 µg/mL). Furthermore, compound 1 displayed moderate level of cytotoxicity on NIH-3 T3 cells, with IC₅₀ = 5.8 ± 0.3 µg/mL compared to the cyclohexamide IC₅₀ = 0.13 ± 0.02 µg/mL. Compound 3 showed lower antifungal activity on Candida krusei and Candida glabrata, MIC of 125 μg/mL on each strain compared to 50 μg/mL for fuconazole. The extracts showed low antifungal activities ranging from 250 to 500 μg/mL on C. albicans, C. krusei and C. glabrata and the values of MIC on Candida parapsilosis were 500 μg/mL and above. DPPH* scavenging activity was exhibited by compounds 1 (IC₅₀ = 15.653 ± 0.335 μg/mL) and 3 (IC₅₀ = 89.077 ± 24.875 μg/mL) compared to Vitamin C (IC₅₀ = 3.343 ± 0.271 μg/mL) while extracts showed moderate antiradical activities with IC₅₀ values ranging from 309.31 ± 2.465 to 635.52 ± 11.05 µg/mL. These results indicate that compounds 1, 6 and 9 are potent anti-inflammatory drug candidates while 1 and 3 could be potent antioxidant drugs.     

Withaphysalin-type withanolides from Physalis minima

Nine new withaphysalin-type withanolides (1–9), named physaminimins (G-O) were isolated from the whole plants of Physalis minima Linn. The structures of these compounds were elucidated based on spectroscopic methods (1D NMR, HSQC, HMBC, ROESY) and HRESIMS. Physaminimins G, H, and K showed inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a macrophage (RAW264.7) cells with IC₅₀ values of 17.41 ± 1.04, 36.33 ± 1.95 and 21.48 ± 1.67 μM, respectively.     

A new megastigmane from Kalanchoe tubiflora (Harvey) Hamet

One new megastigmane, (6S,7R,8R,9S)-6-oxaspiro-7,8-dihydroxymegastigman-4-en-3-one (1) (tubiflorone, 1), and ten known compounds were isolated and characterized from the EtOH extract of Kalanchoe tubiflora (Harvey) Hamet. Structures of these isolates were assigned based on spectroscopic analyses that included 1D and 2D NMR techniques, such as HMQC, HMBC, and NOESY. The anti-inflammatory activities of selected isolated compounds (1–6 and 9–11) were evaluated as inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cell lines. Compounds 1–4, 6, 9, and 11 possessed nitric oxide inhibitory activity with IC₅₀ values ranging from 15.1 ± 0.9 to 98.9 ± 1.3 μM.     

Two new azaphilones from the marine-derived fungus Penicillium sclerotiorum E23Y-1A

Two new azaphilones, penicilazaphilones F (1) and G (2) together with two known analogs (3 and 4), were isolated from fermentation cultures of the marine-derived fungus Penicillium sclerotiorum E23Y-1A. Their structures were elucidated based on spectroscopic methods, including IR, MS, 1D and 2D NMR, as well as by comparison with published data. The absolute configuration of compound 1 was unambiguously determined using electronic circular dichroism (ECD) calculation. All isolated compounds were evaluated for their anti-inflammatory effects. Compounds 1-4 inhibited the lipopolysaccharide-induced production of nitric oxide (NO) in BV-2 cells, with IC₅₀ values of 31.7 ± 1.5, 34.5 ± 1.4, 25.3 ± 2.2, and 34.8 ± 1.9 μM, respectively. In contrast, these compounds showed no obvious cytotoxicity at a concentration of 50.0 μM.     

Anti-inflammatory secoiridoid glycosides from Gentianella azurea

A phytochemical investigation on crude extract of Gentianella azurea led to the isolation of ten new (1–10) and one known (11) secoiridoid glycosides. Their structures were unambiguously elucidated by analysis of 1D and 2D NMR. Compounds 2, 5 and 11 were found to inhibit nitric oxide (NO) production in RAW 264.7 macrophages with IC₅₀ values of 52.78 ± 8.61, 0.69 ± 0.23 and 5.18 ± 1.33, respectively, while indomethacin, the positive control, showed an IC₅₀ value of 1.25 ± 0.52 μM.     

Chemical constituents from Abrus cantoniensis and their cytotoxic effects on cancer cells

Two new compounds named 4-(4-hydroxybenzyl)-isofraxidin (1) and 1''-methoxyl-bavacoumestan B (2), along with five known compounds (3–7) were isolated from the EtOAc-soluble extract of Abrus cantoniensis. Their structures were elucidated with spectroscopic and physico-chemical analyses. All isolates were evaluated for their cytotoxic activities against four cancer cell lines including HepG2, SMMC-7721, A549 and MCF-7. Among them, compounds 1 and 5 exhibited significant cytotoxic activity on the above four cell lines. In particular, 1 showed the potent cytotoxic activity on HepG2 and SMMC-7721 cells with IC₅₀ values of 4.31 ± 0.5 and 3.24 ± 0.9 μM, respectively.     

Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities

A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and another flavone glycoside with spectroscopic data reported for the first time, kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1→6)]-β-d-glucoside (3), along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B with IC₅₀ values of 7.14 ± 1.75 and 7.73 ± 0.24 μM, respectively. In addition, compound 1 showed significant inhibitory effect with an IC₅₀ value of 17.03 ± 0.09 μM. Furthermore, these compounds were tested in AChE inhibitory assays. Most of them were found to have moderate inhibitory effects, with IC₅₀ values ranging from 60.20 ± 1.09 to 92.85 ± 1.12 μM. Except compounds 3, 8, and 18 were inactive.     

Chemical constituents of Mussaenda erythrophylla Schumach. & Thonn. (Rubiaceae) and their chemophenetic significance

The chemical investigation of the CH₂Cl₂/MeOH (1:1) extract from the aerial part of Mussaenda erythrophylla Schumach. & Thonn. (Rubiaceae) resulted in the isolation of sixteen known compounds (1–16) distributed in coumarins, flavonoid glucosides, quinic acid derivatives, triterpenoids, monoglycerid, steroids, tetraterpenoid and polyol. The structures of the compounds were determined by spectrometric and spectroscopic analysis including MS and NMR data followed by their comparison with reported ones in the literature. The chemophenetic significance of the isolated compounds was discussed. The crude extract and some of the isolated compounds were assessed in vitro for their antileishmanial, cytotoxic and antiplasmodial activities. The crude extract of M. erythrophylla showed moderate antileishmanial activity (IC₅₀ = 61.6 μg/mL) while the hexane soluble fraction showed good antileishmanial activity (IC₅₀ = 31.06 μg/mL) compared to the reference drug amphotericin B (IC₅₀ = 0.11 μM). Compounds 11 and 9 also exhibited potent antileishmanial activity (IC₅₀ = 53.7–52.0 μM). The crude extract as well as the ethyl acetate soluble fraction also exhibited good antiplasmodial activity (IC₅₀ = 7.43 ± 0.00 μg/mL and 14.49 ± 2.96 μg/mL respectively), while compounds 11, 15 and 16 showed weak activity with IC₅₀ > 20 μM compared to the reference drug artemisinin (IC₅₀ = 0.014 ± 0.001 μM).     

Synthesis and anti-inflammatory activity of 2-oxo-2H-chromenyl and 2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates

Cycloaddition reaction of 4-chloro-2-oxo-2H-chromene-3-carbaldehydes (3a-g) and 4-chloro-2H-chromene-3-carbaldehydes (7a-h) with activated alkynes (4a-b) provided the 2-oxo-2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates (5a-n) and 2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates (8a-p). All the prepared compounds were screened for anti-inflammatory activity. In vitro anti-inflammatory activity data demonstrated that the compounds 5g, 5i, 5k-l and 8f are effective among the tested compounds against TNF-α (1.108 ± 0.002, 0.423 ± 0.022, 0.047 ± 0.001, 0.070 ± 0.002 and 0.142 ± 0.001 µM) in comparison with standard compound Prednisolone (0.033 ± 0.002 µM). Based on in vitro results, three compounds (5i, 5k and 8f) have been selected for in vivo experiments and these compounds are identified as better compounds with respect to anti-inflammatory activity in LPS induced mice model. Compound 5i was identified as potent and showed significant reduction in TNF-α and IL-6.     

Syntheses,in vitro α-amylase and α-glucosidase dual inhibitory activities of 4-amino-1,2,4-triazole derivatives their molecular docking and kinetic studies

Thirty-three 4-amino-1,2,4-triazole derivatives 1–33 were synthesized by reacting 4-amino-1,2,4-triazole with a variety of benzaldehydes. The synthetic molecules were characterized via ¹H NMR and EI-MS spectroscopic techniques and evaluated for their anti-hyperglycemic potential. Compounds 1–33 exhibited good to moderate in vitro α-amylase and α-glucosidase inhibitory activities in the range of IC₅₀ values 2.01 ± 0.03–6.44 ± 0.16 and 2.09 ± 0.08–6.54 ± 0.10 µM as compared to the standard acarbose (IC₅₀ = 1.92 ± 0.17 µM) and (IC₅₀ = 1.99 ± 0.07 µM), respectively. The limited structure-activity relationship suggested that different substitutions on aryl part of the synthetic compounds are responsible for variable activity. Kinetic study predicted that compounds 1–33 followed mixed and non-competitive type of inhibitions against α-amylase and α-glucosidase enzymes, respectively. In silico studies revealed that both triazole and aryl ring along with different substitutions were playing an important role in the binding interactions of inhibitors within the enzyme pocket. The synthetic molecules were found to have dual inhibitory potential against both enzymes thus they may serve as lead candidates for the drug development and research in the future studies.     

[RuIII(medtra)(H2O)] (medtra = N-methylethylenediaminetriacetate) complex – A highly efficient NO inhibitor with low toxicity

Stopped-flow kinetic measurements were used to compare the reactivities of [Ru(medtra)(H₂O)] (medtra³⁻ = N-methylethylenediaminetriacetate) (1) and [Ru(hedtra)(H₂O)] (2) (hedtra³⁻ = N-hydroxyethylethylenediaminetriacetate) with NO in aqueous solution at 15 °C, pH 7.2 (phosphate buffer). The measured second-order rate constants (3 × 10³ and 6 × 10⁴ M⁻¹ s⁻¹ for 1 and 2, respectively) are three to four order of magnitudes lower than that for the reaction between [Ru^III(edta)(H₂O)]⁻ (3) with NO. However, NO scavenging studies of complexes 1–3, conducted by measuring the difference in nitrite production between treated and untreated murine macrophage cells, revealed that despite being less kinetically reactive toward NO, the [Ru(medtra)(H₂O)] complex exhibited the highest NO scavenging ability and lowest toxicity of compounds 1–3.     

Diarylheptanoids from the fruits of Amomum kravanh and their inhibitory activities of nitric oxide production

Two new diarylheptanoids with a tetrahydropyran ring, kravanhol A (1) and kravanhol B (2), along with one known diarylheptanoid renealtin A (3) were isolated from the fruits of Amomum kravanh. The structures of compounds 1 and 2 were established by analysis of spectroscopic data and their absolute configurations were determined by Mosher's method and CD experiments. Compound 2 showed inhibitory effect on nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages with an IC₅₀ value of 38.9 ± 1.8 μM.     

Rearranged limonoids and chromones from Harrisonia perforata and their anti-inflammatory activity

Two new rearranged limonoids, harperforatin (1) and harperfolide (2), and a new chromone, harperamone (3), were isolated from fruits and roots of Harrisonia perforata, together with eight known compounds. Their structures were elucidated on the basis of spectroscopic data. Harperfolide (2) exhibited potent anti-inflammatory activity by suppressing nitric oxide (NO) production from activated macrophages with IC₅₀ value of 6.51 μM. Furthermore, its effect is mediated by reduction of iNOS protein expression, attributable to the inhibitory action of LPS-induced NO production.     

A new lignan and a new alkaloid,and α-glucosidase inhibitory compounds from the grains of Echinochloa utilis Ohwi & Yabuno

A new lignan, utilisin (1), and a new alkaloid, echinoutilin (2), together with eleven known compounds 3–13 were isolated from the grains of Echinochloa utilis Ohwi & Yabuno. Their structures were identified through the analysis of spectroscopic data. The absolute configuration of 2 was determined by Mosher’s method. These compounds were evaluated for α-glucosidase inhibitory activity. Among them, compounds 2, 3 and 6 exhibited considerable α-glucosidase inhibitory activity with IC₅₀ values of 42.1 ± 1.3, 58.9 ± 3.7, and 40.9 ± 1.1 μM, respectively. The results indicate that the grains of E. utilis will be useful in the treatment of diabetes control agents.