Proposed Mechanism for the Antitrypanosomal Activity of Quercetin and Myricetin Isolated from Hypericum afrum Lam.: Phytochemistry,In Vitro Testing and Modeling Studies

The in vitro activity of L. donovani (promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells) and T. brucei, from the fractions obtained from the hydroalcoholic extract of the aerial part of Hypericum afrum and the isolated compounds, has been evaluated. The chloroform, ethyl acetate and n-butanol extracts showed significant antitrypanosomal activity towards T. brucei, with IC₅₀ values of 12.35, 13.53 and 12.93 µg/mL and with IC₉₀ values of 14.94, 19.31 and 18.67 µg/mL, respectively. The phytochemical investigation of the fractions led to the isolation and identification of quercetin (1), myricitrin (2), biapigenin (3), myricetin (4), hyperoside (5), myricetin-3-O-β-d-galactopyranoside (6) and myricetin-3’-O-β-d-glucopyranoside (7). Myricetin-3’-O-β-d-glucopyranoside (7) has been isolated for the first time from this genus. The chemical structures were elucidated by using comprehensive one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic data, as well as high-resolution electrospray ionization mass spectrometry (HR-ESI–MS). These compounds have also been evaluated for their antiprotozoal activity. Quercetin (1) and myricetin (4) showed noteworthy activity against T. brucei, with IC₅₀ and IC₉₀ values of 7.52 and 5.71 µM, and 9.76 and 7.97 µM, respectively. The T. brucei hexokinase (TbHK1) enzyme was further explored as a potential target of quercetin and myricetin, using molecular modeling studies. This proposed mechanism assists in the exploration of new candidates for novel antitrypanosomal drugs.     

Polyphenolic Profile of Callistemon viminalis Aerial Parts: Antioxidant,Anticancer and In Silico 5-LOX Inhibitory Evaluations

Five new compounds viz kaempferol 3-O-(4″-galloyl)-β-d-glucopyranosyl-(1‴→6″)-O-β-d-glucopyranoside (1), kaempferol 3-O-β-d-mannuronopyranoside (2), kaempferol 3-O-β-d-mannopyranoside (3), quercetin 3-O-β-d-mannuronopyranoside (4), 2, 3 (S)- hexahydroxydiphenoyl]-d-glucose (5) along with fifteen known compounds were isolated from 80% aqueous methanol extract (AME) of C. viminalis. AME and compounds exerted similar or better antioxidant activity to ascorbic acid using DPPH, O₂⁻, and NO inhibition methods. In addition, compounds 16, 4, and 7 showed cytotoxic activity against MCF-7 cell lines while 3, 7 and 16 exhibited strong activity against HepG2. An in silico analysis using molecular docking for polyphenolic compounds 2, 3, 7, 16 and 17 against human stable 5-LOX was performed and compared to that of ascorbic acid and quercetin. The binding mode as well as the enzyme-inhibitor interactions were evaluated. All compounds occupied the 5-LOX active site and showed binding affinity greater than ascorbic acid or quercetin. The data herein suggest that AME, a source of polyphenols, could be used against oxidative-stress-related disorders.     

New Flavone C-Glycosides from Scleranthus perennis and Their Anti-Collagenase Activity

Three new flavone glycosides, one known flavone glycoside, and the phenolic derivative apiopaenonside were isolated and identified from the ethyl acetate fraction of the aerial parts of Scleranthus perennis. The planar structures were elucidated through extensive analysis of UV-Vis, IR, and ¹H NMR and ¹³C NMR spectral data, including the 2D techniques COSY, HSQC, and HMBC, as well as ESI mass spectrometry. The isolated compounds were established as 5,7,3′-trihydroxy-4′-acetoxyflavone-8-C-β-d-xylopyranoside-2′′-O-glucoside (1), 5,7,3′-trihydroxy-4′-methoxyflavone-8-C-β-d-xylopyranoside-2′′-O-glucoside (2), 5,7-dihydroxy-3′-methoxy-4′-acetoxyflavone-8-C-β-d-xylopyranoside-2′′-O-glucoside (3), 5,7-dihydroxy-3′-methoxy-4′-acetoxyflavone-8-C-β-d-xylopyranoside-2′′-O-(4′′′-acetoxy)-glucoside (4), and apiopaenonside (5). Moreover, all isolated compounds were evaluated for anti-collagenase activity. All compounds exhibited moderate inhibitory activity with IC₅₀ values ranging from 36.06 to 70.24 µM.     

Flavonoid Constituents and Alpha-Glucosidase Inhibition of Solanum stramonifolium Jacq. Inflorescence with In Vitro and In Silico Studies

Solanum stramonifolium Jacq. (Solanaceae) is widely found in South East Asia. In Thailand, it is used as vegetable and as a component in traditional recipes. The results of an alpha-glucosidase inhibitory screening test found that the crude extract of S. stramonifolium inflorescence exhibited the potential effect with IC₅₀ 81.27 μg/mL. The separation was performed by the increasing solvent polarity method. The ethyl acetate, ethanol, and water extracts of S. stramonifolium inflorescence showed the synergistic effect together with acarbose standard. The phytochemical investigation of these extracts was conducted by chromatographic and spectroscopic techniques. Six flavonoid compounds, myricetin 3, 4′, 5′, 7-tetramethyl ether (1), combretol (2), kaempferol (3), kaempferol 7-O-glucopyranoside (4), 5-hydroxy 3-7-4′-5′-tetramethoxyflavone-3′-O-glucopyranoside (5), and a mixture (6) of isorhamnetin 3-O-glucopyranoside (6a) and astragalin (6b) were isolated. This discovery is the first report of flavonoid-glycoside 5. Moreover, the selected flavonoids, kaempferol and astragalin, were representatives to explore the mechanism of action. Both of them performed mixed-type inhibition. The molecular docking gave a better understanding of flavonoid compounds’ ability to inhibit the alpha-glucosidase enzyme.     

In Vitro Screening for Anti-Acetylcholinesterase and Antioxidant Activities of Hottonia palustris L. Extracts and Their Unusual Flavonoids

Hottonia palustris L. is from the genus Hottonia (Primulaceae), and the understanding of its phytochemical and pharmacological properties is limited. In this study, the use of chromatographic techniques led to the isolation of a further eleven compounds, including three new flavonoids: 2′,5-dihydroxyflavone 2′-O-β-glucopyranoside, 5,6-dihydroxyflavone 6-O-(6”-O-glucopyranosyl)-β-glucopyranoside (hottonioside A), and 4′,5,7-trihydroxyflavone 7-O-(2”-O-β-glucuronide)-β-glucopyranoside. Their structures were determined using extensive 1D and 2D NMR data and mass spectrometry (HRMS). The qualitative assessment of the chemical composition of the investigated extracts and fractions was performed using the LC-HRMS technique. Furthermore, the antioxidant potential of extracts, fractions, and compounds and their ability to inhibit acetylcholinesterase were also evaluated. Thus, we may conclude that the observed biological effects are the result of the presence of many biologically active compounds, of which dibenzoylmethane is the most active. Therefore, H. palustris is a source of substances with desirable properties in the prevention and treatment of neurodegenerative diseases.     

A New Xanthone Glycoside from Mangifera indica L.: Physicochemical Properties and In Vitro Anti-Skin Aging Activities

A new xanthone glycoside, 1,3,5,6-tetrahydroxyxanthone-C-4-β-d-glucopyranoside was isolated from the methanol extract of Mangifera indica leaves (Anacardiaceae) growing in Egypt. The structure was clarified by 1D and 2D-NMR spectroscopic data. The physicochemical properties of the compound such as lipophilicity, solubility, and formulation considerations were predicted via in silico ADMET technique using the SwissADME server. This technique provided Lipinski’s rule of five, such as GIT absorption, distribution, metabolism, and skin permeation. The in vitro inhibitory activities against aging-mediated enzymes such as collagenase, elastase, hyaluronidase, and tyrosinase were assessed. The compound exhibited remarkable anti-collagenase, anti-elastase, anti-hyaluronidase, and anti-tyrosinase effects with IC₅₀ values of 1.06, 419.10, 1.65, and 0.48 µg/mL, respectively, compared to the positive control. The compound showed promising predicted aqueous solubility and reasonable skin penetration suggesting the suitability of the compound for topical formulation as an anti-aging agent for cosmetic preparations.     

Phenolic Compounds from Mori Cortex Ameliorate Sodium Oleate-Induced Epithelial–Mesenchymal Transition and Fibrosis in NRK-52e Cells through CD36

Lipid deposition in the kidney can cause serious damage to the kidney, and there is an obvious epithelial–mesenchymal transition (EMT) and fibrosis in the late stage. To investigate the interventional effects and mechanisms of phenolic compounds from Mori Cortex on the EMT and fibrosis induced by sodium oleate-induced lipid deposition in renal tubular epithelial cells (NRK-52e cells), and the role played by CD36 in the adjustment process, NRK-52e cells induced by 200 μmol/L sodium oleate were given 10 μmoL/L moracin-P-2″-O-β-d-glucopyranoside (Y-1), moracin-P-3′-O-β-d-glucopyranoside (Y-2), moracin-P-3′-O-α-l-arabinopyranoside (Y-3), and moracin-P-3′-O-[β-glucopyranoside-(1→2)arabinopyranoside] (Y-4), and Oil Red O staining was used to detect lipid deposition. A Western blot was used to detect lipid deposition-related protein CD36, inflammation-related protein (p-NF-κB-P65, NF-κB-P65, IL-1β), oxidative stress-related protein (NOX1, Nrf2, Keap1), EMT-related proteins (CD31, α-SMA), and fibrosis-related proteins (TGF-β, ZEB1, Snail1). A qRT-PCR test detected inflammation, EMT, and fibrosis-related gene mRNA levels. The TNF-α levels were detected by ELISA, and the colorimetric method was used to detects SOD and MDA levels. The ROS was measured by flow cytometry. A high-content imaging analysis system was applied to observe EMT and fibrosis-related proteins. At the same time, the experiment silenced CD36 and compared the difference between before and after drug treatment, then used molecular docking technology to predict the potential binding site of the active compounds with CD36. The research results show that sodium oleate can induce lipid deposition, inflammation, oxidative stress, and fibrosis in NRK-52e cells. Y-1 and Y-2 could significantly ameliorate the damage caused by sodium oleate, and Y-2 had a better ameliorating effect, while there was no significant change in Y-3 or Y-4. The amelioration effect of Y-1 and Y-2 disappeared after silencing CD36. Molecular docking technology showed that the Y-1 and Y-2 had hydrogen bonds to CD36 and that, compared with Y-1, Y-2 requires less binding energy. In summary, moracin-P-2″-O-β-d-glucopyranoside and moracin-P-3′-O-β-d-glucopyranoside from Mori Cortex ameliorated lipid deposition, EMT, and fibrosis induced by sodium oleate in NRK-52e cells through CD36.     

Determination of Flavonoids in Selected Scleranthus Species and Their Anti-Collagenase and Antioxidant Potential

A new 5,7-dihydroxy-3′-methoxy-4′-acetoxyflavone-8-C-β-d-arabinopyranoside-2″-O-(4‴-acetoxy)-glucoside (6) and three known flavone C-glycosides—5,7,3′,4′-tetrahydroxyflavone-6-C-xyloside-8-C-β-d-glucoside (lucenin-1) (7), 5,7,3′-trihydroxyflavone-6-C-glucoside-8-C-β-d-glucoside (vicenin-2) (8), and 5,7,4′-trihydroxy-3′-methoxyflavone-6-C-β-d-glucopyranoside-8-C-α-arabinopyranoside (chrysoeriol-6-C-β-d-glucopyranoside-8-C-α-arabinopyranoside) (9)—were isolated from aerial parts of Scleranthus perennis L. (Caryophyllaceae). Their structures were determined through the use of comprehensive spectroscopic and spectrometric methods, and a method for the quantification of the major constituents of S. perennis and S. annuus L. was developed. Furthermore, the anti-collagenase and antioxidant activities of all isolated compounds obtained from extracts and fractions from both Scleranthus species were evaluated. The highest percentage of collagenase inhibition (at 400 µg/mL) was distinguished for methanolic extracts (22.06%, 32.04%) and ethyl acetate fractions (16.59%, 14.40%) from S. annuus and S. perennis. Compounds 6–9 displayed moderate inhibitory activity, with IC₅₀ values ranging from 39.59–73.86 µM.     

Phytochemistry and Biological Activities of Iris Species Growing in Iraqi Kurdistan and Phenolic Constituents of the Traditional Plant Iris postii

A dozen Iris species (Iridaceae) are considered traditional remedies in Kurdistan, especially for treating inflammations. Phytochemical studies are still scarce. The information reported in the literature about Iris species growing in Kurdistan has been summarized in the first part of this paper, although, except for Iris persica, investigations have been performed on vegetal samples collected in countries different from Kurdistan. In the second part of the work, we have investigated, for the first time, the contents of the methanolic extracts of Iris postii aerial parts and rhizomes that were collected in Kurdistan. Both extracts exhibited a significant dose-dependent free radical scavenging and total antioxidant activities, comparable to those of ascorbic acid. Medium-pressure liquid chromatographic separations of the two extracts afforded l-tryptophan, androsin, isovitexin, swertisin, and 2″-O-α-l-rhamnopyranosyl swertisin from the aerial parts, whereas ε-viniferin, trans-resveratrol 3,4′-O-di-β-d-glucopyranoside, and isotectorigenin were isolated from the rhizomes. This is the first finding of the last three metabolites from an Iris species. The various remarkable biological activities of isolated compounds scientifically sustain the traditional use of I. postii as a medicinal plant.     

Structure Revision of Isocereulide A,an Isoform of the Food Poisoning Emetic Bacillus cereus Toxin Cereulide

The emetic Bacillus cereus toxin cereulide presents an enormous safety hazard in the food industry, inducing emesis and nausea after the consumption of contaminated foods. Additional to cereulide itself, seven structurally related isoforms, namely the isocereulides A–G, have already been elucidated in their chemical structure and could further be identified in B. cereus contaminated food samples. The newly performed isolation of isocereulide A allowed, for the first time, 1D- and 2D-NMR spectroscopy of a biosynthetically produced isocereulide, revealing results that contradict previous assumptions of an l-O-Leu moiety within its chemical structure. By furthermore applying posthydrolytical dipeptide analysis, amino acid and α-hydroxy acid analysis by means of UPLC-ESI-TOF-MS, as well as MSⁿ sequencing, the structure of previously reported isocereulide A could be corrected. Instead of the l-O-Leu as assumed to date, one l-O-Ile unit could be verified in the cyclic dodecadepsipeptide, revising the structure of isocereulide A to [(d-O-Leu-d-Ala-l-O-Val-l-Val)₂(d-O-Leu-d-Ala-l-O-Ile-l-Val)].     

Synthesis and Antiviral Evaluation of Nucleoside Analogues Bearing One Pyrimidine Moiety and Two D-Ribofuranosyl Residues

A series of 1,2,3-triazolyl nucleoside analogues in which 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via polymethylene linkers to both nitrogen atoms of the heterocycle moiety (uracil, 6-methyluracil, thymine, quinazoline-2,4-dione, alloxazine) or to the C-5 and N-3 atoms of the 6-methyluracil moiety was synthesized. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. Antiviral assays revealed three compounds, 2i, 5i, 11c, which showed moderate activity against influenza virus A H1N1 with IC₅₀ values of 57.5 µM, 24.3 µM, and 29.2 µM, respectively. In the first two nucleoside analogues, 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via butylene linkers to N-1 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine, respectively). In nucleoside analogue 11c, two 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached via propylene linkers to the C-5 and N-3 atoms of the 6-methyluracil moiety. Almost all synthesized 1,2,3-triazolyl nucleoside analogues showed no antiviral activity against the coxsackie B3 virus. Two exceptions are 1,2,3-triazolyl nucleoside analogs 2f and 5f, in which 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached to the C-5 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine respectively). These compounds exhibited high antiviral potency against the coxsackie B3 virus with IC₅₀ values of 12.4 and 11.3 µM, respectively, although both were inactive against influenza virus A H1N1. According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 2i, 5i, and 11c against the H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRp). As to the antiviral activity of nucleoside analogs 2f and 5f against coxsackievirus B3, it can be explained by their interaction with the coat proteins VP1 and VP2.     

Isolation,Characterization and In Silico Studies of Secondary Metabolites from the Whole Plant of Polygala inexpectata Peşmen & Erik

Polygala species are frequently used worldwide in the treatment of various diseases, such as inflammatory and autoimmune disorders as well as metabolic and neurodegenerative diseases, due to the large number of secondary metabolites they contain. The present study was performed on Polygala inexpectata, which is a narrow endemic species for the flora of Turkey, and resulted in the isolation of nine known compounds, 6,3′-disinapoyl-sucrose (1), 6-O-sinapoyl,3′-O-trimethoxy-cinnamoyl-sucrose (tenuifoliside C) (2), 3′-O-(O-methyl-feruloyl)-sucrose (3), 3′-O-(sinapoyl)-sucrose (4), 3′-O-trimethoxy-cinnamoyl-sucrose (glomeratose) (5), 3′-O-feruloyl-sucrose (sibiricose A5) (6), sinapyl alcohol 4-O-glucoside (syringin or eleutheroside B) (7), liriodendrin (8), and 7,4′-di-O-methylquercetin-3-O-β-rutinoside (ombuin 3-O-rutinoside or ombuoside) (9). The structures of the compounds were determined by the spectroscopic methods including 1D-NMR (¹H NMR, ¹³C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC), and HRMS. The isolated compounds were shown in an in silico setting to be accommodated well within the inhibitor-binding pockets of myeloperoxidase and inducible nitric oxide synthase and anchored mainly through hydrogen-bonding interactions and π-effects. It is therefore plausible to suggest that the previously established anti-inflammatory properties of some Polygala-derived phytochemicals may be due, in part, to the modulation of pro-inflammatory enzyme activities.     

Anti-Inflammatory,Antidiabetic Properties and In Silico Modeling of Cucurbitane-Type Triterpene Glycosides from Fruits of an Indian Cultivar of Momordica charantia L.

Diabetes mellitus is a chronic disease and one of the fastest-growing health challenges of the last decades. Studies have shown that chronic low-grade inflammation and activation of the innate immune system are intimately involved in type 2 diabetes pathogenesis. Momordica charantia L. fruits are used in traditional medicine to manage diabetes. Herein, we report the purification of a new 23-O-β-d-allopyranosyl-5β,19-epoxycucurbitane-6,24-diene triterpene (charantoside XV, 6) along with 25ξ-isopropenylchole-5(6)-ene-3-O-β-d-glucopyranoside (1), karaviloside VI (2), karaviloside VIII (3), momordicoside L (4), momordicoside A (5) and kuguaglycoside C (7) from an Indian cultivar of Momordica charantia. At 50 µM compounds, 2–6 differentially affected the expression of pro-inflammatory markers IL-6, TNF-α, and iNOS, and mitochondrial marker COX-2. Compounds tested for the inhibition of α-amylase and α-glucosidase enzymes at 0.87 mM and 1.33 mM, respectively. Compounds showed similar α-amylase inhibitory activity than acarbose (0.13 mM) of control (68.0–76.6%). Karaviloside VIII (56.5%) was the most active compound in the α-glucosidase assay, followed by karaviloside VI (40.3%), while momordicoside L (23.7%), A (33.5%), and charantoside XV (23.9%) were the least active compounds. To better understand the mode of binding of cucurbitane-triterpenes to these enzymes, in silico docking of the isolated compounds was evaluated with α-amylase and α-glucosidase.     

Synthesis and Antiproliferative Evaluation of 2-Deoxy-N-glycosylbenzotriazoles/imidazoles

A series of 2-deoxy-2-iodo-α-d-mannopyranosylbenzotriazoles was synthesized using the benzyl, 4,6-benzylidene and acetyl protected D-glucal in the presence of N-iodosuccinimide (NIS). Subsequent removal of the iodine at the C-2 position using tributyltin hydride under free radical conditions afforded the 2-deoxy-α-d-glucopyranosylbenzotriazoles in moderate to high yields. This method was extended to the preparation of substituted 2-deoxy-β-d-glucopyranosylimidazoles as well. The stereoselectivity of the addition reaction and the effect of the protecting group and temperature on anomer distribution of the benzotriazole series were also investigated. The anticancer properties of the newly synthesized compounds were evaluated in a series of viability studies using HeLa (human cervical adenocarcinoma), human breast and lung cancer cell lines. The N-[3,4,6-tri-O-benzyl-2-deoxy-α-d-glucopyranosyl]-1H-benzotriazole and the N-[3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl]-2H-benzotriazole were found to be the most potent cancer cell inhibitors at 20 µM concentrations across all four cell lines.     

Purification,Structural Characterization and Immunomodulatory Effects of Polysaccharides from Amomum villosum Lour. on RAW 264.7 Macrophages

Amomum Villosum Lour. (A. villosum) is a folk medicine that has been used for more than 1300 years. However, study of the polysaccharides of A. villosum is seriously neglected. The objectives of this study are to explore the structural characteristics of polysaccharides from A. villosum (AVPs) and their effects on immune cells. In this study, the acidic polysaccharides (AVPG-1 and AVPG-2) were isolated from AVPs and purified via anion exchange and gel filtration chromatography. The structural characteristics of the polysaccharides were characterized by methylation, HPSEC-MALLS-RID, HPLC, FT-IR, SEM, GC-MS and NMR techniques. AVPG-1 with a molecular weight of 514 kDa had the backbone of → 4)-α-d-Glcp-(1 → 3,4)-β-d-Glcp-(1 → 4)-α-d-Glcp-(1 →. AVPG-2 with a higher molecular weight (14800 kDa) comprised a backbone of → 4)-α-d-Glcp-(1 → 3,6)-β-d-Galp-(1 → 4)-α-d-Glcp-(1 →. RAW 264.7 cells were used to investigate the potential effect of AVPG-1 and AVPG-2 on macrophages, and lipopolysaccharide (LPS) was used as a positive control. The results from bioassays showed that AVPG-2 exhibited stronger immunomodulatory activity than AVPG-1. AVPG-2 significantly induced nitric oxide (NO) production as well as the release of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), and upregulated phagocytic capacities of RAW 264.7 cells. Real-time PCR analysis revealed that AVPG-2 was able to turn the polarization of macrophages to the M1 direction. These results suggested that AVPs could be explored as potential immunomodulatory agents of the functional foods or complementary medicine.     

Microbial Transformation and Biological Activities of the Prenylated Aromatic Compounds from Broussonetia kazinoki

Broussonetia kazinoki has been used as a traditional medicine for the treatment of burns and acne, and its extracts have been found to show tyrosinase inhibitory and anticancer activities. In this study, the tyrosinase inhibitory and cytotoxic activities of B. kazinoki were explored, leading to the isolation of kazinol C (1), kazinol E (2), kazinol F (3), broussonol N (4), and kazinol X (5), of which the compounds 4 and 5 have not been previously reported. Microbial transformation has been recognized as an efficient tool to generate more active metabolites. Microbial transformation of the major compounds 1 and 3 was conducted with Mucor hiemalis, where four glucosylated metabolites (6–9) were produced from 1, while one hydroxylated (10) and one glucosylated (11) metabolites were obtained from 3. Structures of the isolated metabolites were determined by extensive spectroscopic analyses. All compounds were evaluated for their tyrosinase inhibitory and cytotoxic activities. Compound 3 and its metabolites, kazinol Y (10) and kazinol F-4″-O-β-d-glucopyranoside (11), exhibited the most potent tyrosinase inhibitory activities with the IC₅₀ values ranging from 0.71 to 3.36 µM. Meanwhile, none of the metabolites, except for kazinol C-2′,3″-di-O-β-d-glucopyranoside (7), showed moderate cytotoxic activities (IC₅₀ 17.80 to 24.22 µM) against A375P, B16F10 and B16F1 cell lines.     

New Terpenoids from Potentilla freyniana Bornm. and Their Cytotoxic Activities

Two new A-ring contracted triterpenoids, madengaisu A and madengaisu B, and one undescribed ent-kaurane diterpenoid, madengaisu C, along with 20 known compounds were isolated from the roots of Potentilla freyniana Bornm. The structures were elucidated using extensive spectroscopic techniques, including 1D and 2D-NMR, HR-ESI-MS, ECD spectra, IR, and UV analysis. Moreover, all isolated constituents were evaluated for their anti-proliferative activity against RA-FLS cells and cytotoxic activities against the human cancer cell lines Hep-G2, HCT-116, BGC-823, and MCF-7. Ursolic acid and pomolic acid displayed moderate inhibitory activity in RA-FLS cells with IC₅₀ values of 24.63 ± 1.96 and 25.12 ± 1.97 μM, respectively. Hyptadienic acid and 2α,3β-dihydroxyolean-12-en-28-oic acid 28-O-β-d-glucopyranoside exhibited good cytotoxicity against Hep-G2 cells with IC₅₀ values of 25.16 ± 2.55 and 17.66 ± 1.82 μM, respectively. In addition, 2α,3β-dihydroxyolean-13(18)-en-28-oic acid and alphitolic acid were observed to inhibit HCT-116 cells (13.25 ± 1.65 and 21.62 ± 0.33 μM, respectively), while madengaisu B and 2α,3β-dihydroxyolean-13(18)-en-28-oic acid showed cytotoxic activities against BGC-823 cells with IC₅₀ values of 24.76 ± 0.94 and 26.83 ± 2.52 μM, respectively, which demonstrated that triterpenes from P. freyniana may serve as therapeutic agents for RA and cancer treatment.     

Structural Characterization and Assessment of Anti-Inflammatory and Anti-Tyrosinase Activities of Polyphenols from Melastoma normale

Polyphenols, widely distributed in the genus Melastoma plants, possess extensive cellular protective effects such as anti-inflammatory, anti-tyrosinase, and anti-obesity, which makes it a potential anti-inflammatory drug or enzyme inhibitor. Therefore, the aim of this study is to screen for the anti-inflammatory and enzyme inhibitory activities of compounds from title plant. Using silica gel, MCI, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, the extract of Melastoma normale roots was separated. Four new ellagitannins, Whiskey tannin C (1), 1-O-(4-methoxygalloyl)-6-O-galloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (2), 1-O-galloyl-6-O-(3-methoxygalloyl)-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (3), and 1-O-galloyl-6-O-vanilloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (4), along with eight known polyphenols were firstly obtained from this plant. The structures of all isolates were elucidated by HRMS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW2 64.7 cells, we investigated the anti-inflammatory activities of compounds 1–4, unfortunately, none of them exhibit inhibit nitric oxide (NO) production, their IC₅₀ values are all > 50 μM. Anti-tyrosinase activity assays was done by tyrosinase inhibition activity screening model. Compound 1 showed weak tyrosinase inhibitory activity with IC₅₀ values of 426.02 ± 11.31 μM. Compounds 2–4 displayed moderate tyrosinase inhibitory activities with IC₅₀ values in the range of 124.74 ± 3.12–241.41 ± 6.23 μM. The structure–activity relationships indicate that hydroxylation at C-3′, C-4′, and C-3 in the flavones were key to their anti-tyrosinase activities. The successful isolation and structure identification of ellagitannin provide materials for the screening of anti-inflammatory drugs and enzyme inhibitors, and also contribute to the development and utilization of M. normale.     

A new flavone glycoside from Selaginella moellendorffii Hieron.

From the ethanol extract of Selaginella moellendorffii Hieron., a new flavone O-glycoside and three known flavone C-glycosides have been isolated and identified as 5-carboxymethyl-4′-hydroxyflavone-7-O-β-D-glucopyranoside 1, 6,8-di-C-β-D-glueopyranosylapigenin 2, 6-C-[3-D-glucopyranosyl-8-C-β-D-xylopyranosyl apigenin 3, 6-C-B-D-xylopyranosyl-8-C-β-glucopyranosylapigenin 4, respectively. Their structures were elucidated by spectroscopic methods.     

Validation of the Antioxidant and Enzyme Inhibitory Potential of Selected Triterpenes Using In Vitro and In Silico Studies,and the Evaluation of Their ADMET Properties

The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes’ potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 2′,3′,4′,7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (−7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.