Inhibition of Soluble Epoxide Hydrolase by Cembranoid Diterpenes from Soft Coral Sinularia maxima: Enzyme Kinetics, Molecular Docking, and Molecular Dynamics.

Soluble epoxide hydrolase (sEH) is essential for converting epoxy fatty acids, such as epoxyeicosatrienoic acids (EETs), into their dihydroxy forms. EETs play a crucial role in regulating blood pressure, mediating anti-inflammatory responses, and modulating pain, making sEH a key target for therapeutic interventions. Current research is increasingly focused on identifying sEH inhibitors from natural sources, particularly marine environments, which are rich in bioactive compounds due to their unique metabolic adaptations. In this study, the sEH inhibitory activities of ten cembranoid diterpenes (1-10) isolated from the soft coral Sinularia maxima were evaluated. Among them, compounds 3 and 9 exhibited considerable sEH inhibition, with IC50 values of 70.68 µM and 78.83 µM, respectively. Enzyme kinetics analysis revealed that these two active compounds inhibit sEH through a non-competitive mode. Additionally, in silico approaches, including molecular docking and molecular dynamics simulations, confirmed their stability and interactions with sEH, highlighting their potential as natural therapeutic agents for managing cardiovascular and inflammatory diseases.

Acetylcholinesterase inhibition studies of alkaloid components from Crinum asiaticum var. sinicum: in vitro assessments by molecular docking and molecular dynamics simulations.

Alkaloids are among the most important and best-known secondary metabolites as sources of new drugs from medicinal plants and marine organisms. A phytochemical investigation of the whole plant of Crinum asiaticum var. sinicum resulted in the isolation of seven alkaloids (1-7), including one new dimeric compound, bis-(-)-8-demethylmaritidine (1). Their structures were elucidated using NMR and HR-ESI-MS. The absolute configuration of new compound 1 was established by circular dichroism spectroscopy. All isolated compounds were evaluated for their inhibitory effects on acetylcholinesterase (AChE) activity in vitro. Among them, compound 1 exhibited the most potent AChE inhibition. Moreover, molecular docking and molecular dynamics simulations were carried out for the most active compound to investigate their binding interactions and dynamics behavior of the AChE protein-ligand complex. Therefore, compound 1 may be a potential candidate for effectively treating Alzheimer's disease.

Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia.

Microglia play a significant role in immune defense and tissue repair in the central nervous system (CNS). Microglial activation and the resulting neuroinflammation play a key role in the pathogenesis of neurodegenerative disorders. Recently, inflammation reduction strategies in neurodegenerative diseases have attracted increasing attention. Herein, we discovered and evaluated the anti-neuroinflammatory potential of compounds from the Antarctic fungi strain Aspergillus sp. SF-7402 in lipopolysaccharide (LPS)-stimulated BV2 cells. Four metabolites were isolated from the fungi through chemical investigations, namely, 5-methoxysterigmatocystin (1), sterigmatocystin (2), aversin (3), and 6,8-O-dimethylversicolorin A (4). Their chemical structures were elucidated by extensive spectroscopic analysis and HR-ESI-MS, as well as by comparison with those reported in literature. Anti-neuroinflammatory effects of the isolated metabolites were evaluated by measuring the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in LPS-activated microglia at non-cytotoxic concentrations. Sterigmatocystins (1 and 2) displayed significant effects on NO production and mild effects on TNF-α and IL-6 expression inhibition. The molecular mechanisms underlying this activity were investigated using Western blot analysis. Sterigmatocystin treatment inhibited NO production via downregulation of inducible nitric oxide synthase (iNOS) expression in LPS-stimulated BV2 cells. Additionally, sterigmatocystins reduced nuclear translocation of NF-κB. These results suggest that sterigmatocystins present in the fungal strain Aspergillus sp. are promising candidates for the treatment of neuroinflammatory diseases.

Effect of citric acid and heat treatment on the content of less-polar ginsenosides in flower buds of Panax ginseng.

Ginseng flower bud (GFB), as an inexpensive part of Panax ginseng, attracted significant attention as a beneficial functional food with medicinal potentials due to its high content of ginsenosides. A few studies focused on the utilization of heat treatment and citric acid treatment to process ginseng flowers, converting its polar ginsenosides into rare ginsenosides to improve its biological activities. Thus, in this study, we compared the changes of ginsenosides in GFB after citric acid and heat treatment by HPLC method. The results revealed that less-polar ginsenoside, Rg6 and F4, increased to 1.01 and 0.27% by heat treatment, respectively. Further, ginsenoside F2 increased to 1.13% with 1 M citric acid treatment. Furthermore, based on the combination of these two processing methods for the first time, the conversion rate of less-polar ginsenosides surged to 80%. The content of ginsenoside Rg3(s) and Rg5 increased to 1.509 and 1.871%, respectively, by simultaneous heat and citric acid treatment. Therefore, a processing approach that simultaneously performs heat and citric acid treatments has been proposed, and this considerably inexpensive and convenient processing method could be applied to the processing of GFBs and produce less-polar ginsenosides.

Inhibitory Effects of Cucurbitane-Type Triterpenoids from Momordica charantia Fruit on Lipopolysaccharide-Stimulated Pro-Inflammatory Cytokine Production in Bone Marrow-Derived Dendritic Cells.

The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds responsible for its anti-inflammatory activities. In addition, the in vitro inhibitory effect of M. charantia on pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) has not been reported. Phytochemical investigation of M. charantia fruit led to the isolation of 15 compounds (1-15). Their chemical structures were elucidated spectroscopically (one- and two-dimensional nuclear magnetic resonance) and with electrospray ionization mass spectrometry. The anti-inflammatory effects of the isolated compounds were evaluated by measuring the production of the pro-inflammatory cytokines interleukin IL-6, IL-12 p40, and tumor necrosis factor α (TNF-α) in LPS-stimulated BMDCs. The cucurbitanes were potent inhibitors of the cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Based on these studies and in silico simulations, we determined that the ligand likely docked in the receptors. These results suggest that cucurbitanes from M. charantia are potential candidates for treating inflammatory diseases.

Enhancement of an In Vivo Anti-Inflammatory Activity of Oleanolic Acid through Glycosylation Occurring Naturally in Stauntonia hexaphylla.

Stauntonia hexaphylla (Lardizabalaceae) has been used as a traditional herbal medicine in Korea and China for its anti-inflammatory and analgesic properties. As part of a bioprospecting program aimed at the discovery of new bioactive compounds from Korean medicinal plants, a phytochemical study of S. hexaphylla leaves was carried out leading to isolation of two oleanane-type triterpene saponins, 3-O-[ß-d-glucopyranosyl (1→2)-α-l-arabinopyranosyl] oleanolic acid-28-O-[ß-d-glucopyranosyl (1→6)-ß-d-glucopyranosyl] ester (1) and 3-O-α-l-arabinopyranosyl oleanolic acid-28-O-[ß-d-glucopyranosyl (1→6)-ß-d-glucopyranosyl] ester (2). Their structures were established unambiguously by spectroscopic methods such as one- and two-dimensional nuclear magnetic resonance and infrared spectroscopies, high-resolution electrospray ionization mass spectrometry and chemical reactions. Their anti-inflammatory activities were examined for the first time with an animal model for the macrophage-mediated inflammatory response as well as a cell-based assay using an established macrophage cell line (RAW 264.7) in vitro. Together, it was concluded that the saponin constituents, when they were orally administered, exerted much more potent activities in vivo than their sapogenin core even though both the saponins and the sapogenin molecule inhibited the RAW 264.7 cell activation comparably well in vitro. These results imply that saponins from S. hexaphylla leaves have a definite advantage in the development of oral medications for the control of inflammatory responses.

Isolation, structural elucidation, and insights into the anti-inflammatory effects of triterpene saponins from the leaves of Stauntonia hexaphylla.

Using various chromatographic techniques, 23 triterpene saponins (1-23) were isolated from an ethanol extract of Stauntonia hexaphylla, including two new compounds (12 and 15). Their chemical structures were established by comprehensive spectroscopic methods such as 1D- and 2D-NMR, and HR-ESI-MS, and chemical reactions. The anti-inflammatory activities of the isolated saponins were determined using the nitric oxide (NO) assay. Compound 13 exhibited the greatest inhibitory effect (IC50 = 0.59 µM). In addition to NO, compound 13 suppressed the secretion of PGE2, IL-1ß, and IL-6, but not TNF-α, and inhibited the protein expression of iNOS and COX-2 in LPS-activated RAW264.7 cells. The chemical derivatives of the isolated compounds were studied using structure-activity relationships. The results suggested that compound 13 isolated from S. hexaphylla might be useful for treating inflammation. This is the first comprehensive study of saponins from the leaves of S. hexaphylla based on anti-inflammatory extract screening guidelines.

Chemical constituents from Vietnamese mangrove Calophyllum inophyllum and their anti-inflammatory effects.

In a search for anti-inflammatory activity in resources from Vietnamese mangroves, we found that a methanolic extract from the leaves of Calophyllum inophyllum (CIL) showed significant anti-inflammatory effects in vitro. Using various chromatographic techniques, we subsequently isolated 12 compounds (1-12) from a methanolic extract of CIL, including two novel compounds (1-2). The inhibitory effects of these compounds on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells were also evaluated. Compound 1 significantly suppressed NO production (IC50 = 2.44 ±â€¯0.88 µM), the secretion of pro-inflammatory cytokines (including interleukin-1 beta and tumor necrosis factor alpha), and the expression of inducible nitric oxide synthase through downregulation of nuclear factor-kappa-B signaling cascades. These results suggest that C. inophyllum leaves might be a useful resource for the development of drugs for the treatment of inflammation.

Coral and Coral-Associated Microorganisms: A Prolific Source of Potential Bioactive Natural Products.

Marine invertebrates and their associated microorganisms are rich sources of bioactive compounds. Among them, coral and its associated microorganisms are promising providers of marine bioactive compounds. The present review provides an overview of bioactive compounds that are produced by corals and coral-associated microorganisms, covering the literature from 2010 to March 2019. Accordingly, 245 natural products that possess a wide range of potent bioactivities, such as anti-inflammatory, cytotoxic, antimicrobial, antivirus, and antifouling activities, among others, are described in this review.

Two new dammarane-type triterpene saponins from Korean red ginseng and their anti-inflammatory effects.

Panax ginseng has been the subject of extensive research on potential medicinal materials. The goal of this study was search the chemical constituents and biological activities of processed Panax ginseng, Korean red ginseng. Our efforts led to the isolation eleven compounds (1-11) including two new compounds 1 and 2 from Korean red ginseng using various chromatographic techniques. Chemical structures of isolated compounds were demonstrated by spectroscopic methods (1D-, 2D-NMR, and HR-ESI-MS). The anti-inflammatory effects of the compounds were investigated by inhibiting IL-6 and TNF-α secretion in LPS-activated RAW264.7 cells. Additionally, the effects of the compounds on the expression of COX-2 and iNOS were examined by Western blotting. Compound 1 significantly reduced the level of proinflammatory cytokines IL-6 and TNF-α secretion in LPS-activated RAW264.7 cells and the expression of COX-2 and iNOS inflammatory enzymes in the cells. These results suggested that compound 1, a new ginsenoside might useful in treatment of inflammation.

Steroid glycosides from the starfish Pentaceraster gracilis.

Using combined chromatographic separations, two new steroid glycosides namely pentacerosides A (1) and B (2), and four known compounds were isolated from the methanol extract of the starfish Pentaceraster gracilis. Their structures were determined on the basis of spectroscopic data (1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, ROESY, and FT-ICR-MS) and by comparing obtained results to the literature values. Among the isolated compounds, only maculatoside (5) showed significant cytotoxic effect against Hep-G2 (IC50 = 16.75 ± 0.69 µM) and SK-Mel2 (IC50 = 19.44 ± 1.45 µM) cell lines and moderate effect on KB (IC50 = 36.53 ± 0.78 µM), LNCaP (IC50 = 39.75 ± 3.34 µM), and MCF7 (IC50 = 47.34 ± 7.01 µM) cell lines.

Rat intestinal sucrase inhibited by minor constituents from the leaves and twigs of Archidendron clypearia (Jack.) Nielsen.

In the search for plants, containing compounds with α-glucosidase inhibitory activity, we found that a methanolic extract from the leaves and twigs of Archidendron clypearia (Jack.) Nielsen significantly inhibited rat intestinal sucrase in vitro. A phytochemical investigation of the aqueous layer of an A. clypearia extract led to the isolation of 14 compounds (1-14). Their structures were established through extensive 1D and 2D NMR, CD data, and MS analysis. The methanolic extract, as well as the water layer at a concentration of 3.0mg/mL, showed potent sucrase inhibitory activity, with 67.78±2.53% and 95.33±2.15% inhibition, respectively. In addition, compounds 6, 7, and 10 (1.0mM) showed potent sucrase inhibition (88.36±1.15%, 81.57±1.07%, and 66.32±4.73% inhibition, respectively), which was comparable to that of the positive control, acarbose, which exhibited 89.54±0.91% inhibition. Other compounds showed moderate or weak inhibitory activity at the same concentration. The sucrase inhibitory activity of the extracts and purified compounds may provide a novel opportunity to develop a new class of antidiabetic agents.

Further Highly Hydroxylated Steroids from the Vietnamese Starfish Archaster typicus.

Eight highly hydroxylated steroids (1-8), including three new compounds as sodium salts of (24S)-5α-cholestane-3ß,4ß,5,6α,7ß,8,14,15α,24-nonaol 6-sulfate (1), (24E)-5α-cholest-24-ene-26-yde-3ß,6α,8,14,15α-pentaol 15-sulfate (2), and 5α-cholest-3ß,6α,8,14,15α,24,25,26-octaol 15-sulfate (3), were isolated and elucidated from the methanol extract of the Vietnamese starfish Archaster typicus. The structure elucidation was done by spectroscopic methods including one and two dimensional (1D-, 2D-)NMR and Fourier transform ion cyclotron resonance (FT-ICR)-MS. The isolated compounds can be used as chemical markers for taxonomic identification of the starfish A. typicus.

Traditional Uses, Phytochemistry, and Pharmacological Activities of Vernonia cinerea (L.) Less.: An Updated Review.

Vernonia cinerea (L.) Less. is a perennial herbaceous plant found mainly in tropical areas, particularly in Southeast Asia, South America, and India. Various parts of V. cinerea have traditionally been used in folk medicine to treat several diseases, such as malaria, fever, and liver diseases. V. cinerea has so far yielded about 92 secondary metabolites. The majority of these are sesquiterpene lactones, but triterpenes, flavonoids, steroids, phenolics, and other compounds are present as well. V. cinerea crude extracts reportedly exhibit anti-inflammatory, antiprotozoal, antidiabetic, anticancer, antimicrobial, antioxidant, and renoprotective activities. This study aims to provide the latest up-to-date information on the botanical characterization, distribution, traditional uses, phytochemistry, and pharmacological activity of V. cinerea. Information on V. cinerea was thoroughly reviewed. The literature published between 1950 and 2024 was compiled through online bibliographic databases, including SciFinder, Web of Science, Google Scholar, PubMed, ScienceDirect, Springer Link, Wiley, and the MDPI online library. The keywords used for the literature search included Vernonia cinerea (L.) Less. and the synonyms Cyanthillium cinereum (L.) H.Rob., Conyza cinerea L., and various others.

Identification of Interleukin (IL)-33 Inhibitory Constituents from Canavalia gladiata Pods.

Interleukin (IL)-33, a member of the IL-1 cytokine family, plays a vital role in immune system regulation and inflammation, with oxidative stress being implicated in its expression. During the search for compounds from natural sources with potential as therapeutic agents for allergic diseases via IL-33 signal modulation, we discovered significant IL-33 inhibitory activity in the methanol extract of Canavalia gladiata (sword bean) pods. Through chromatographic separation and liquid chromatography-mass spectrometry, we isolated 11 compounds (1-11) from the methanol extract. Furthermore, we assessed the inhibitory effects of these substances on IL-33/ST2 signaling in processes related to inflammatory and autoimmune diseases using an enzyme-linked immunosorbent assay. Among them, compounds 7, 10, and 11 exhibited substantial IL-33 inhibitory efficacy, with values reaching 78%, 86%, and 79% at 100 µM, respectively. Remarkably, compounds 7, 10, and 11 demonstrated significant and dose-dependent inhibition of IL-33 signaling at concentrations of 10, 50, and 100 µM. Computational molecular docking and dynamic simulations further elucidated the underlying mechanisms. These findings have promising pharmacological implications for allergy prevention and treatment associated with flavonoid glycosides derived from C. gladiata.

Efficacy of Jasminum subtriplinerve Extract against 7,12-Dimethylbenz[a]anthracene-Induced Cancer in Mice.

Jasminum subtriplinerve Blume tea is a traditional Vietnamese medicine used to treat impetigo, menstruation issues, and painful menstrual hematometra. Previous studies have shown that extracts and isolated compounds from J. subtriplinerve possess diverse pharmacological properties, such as antioxidant, antibacterial, and antidiabetic effects. However, their potential anticancer effects and underlying mechanisms of action have not been clear. Here, we examined the effects of J. subtriplinerve extracts against three human cancer cell lines. We also conducted in vivo analyses using a mouse model of 7,12-dimethylbenz[a]anthracene-induced breast cancer, including an investigation of changes in histological sections. The effect of the J. subtriplinerve ethyl acetate fraction on cytokine levels (IL-2, PGE2, TNF-α) in serum was determined using ELISA kits. Results showed that the EtOAc fraction had the highest anti-proliferative activity (IC50 = 13.7 mg/ml) against the breast cancer (MCF-7) cell line, while the BuOH and water fractions did not show any anticancer effects. Additionally, the EtOAc fraction at a dose of 14.4 mg/kg was able to elevate IL-2 levels and suppress the expression of PGE2 in the serum of mice. A remarkable decrease in the percentage of death and tumor incidence in mice was achieved following treatment with the EtOAc fraction at a dose of 14.4 mg/kg. No abnormal parameters in blood were observed in the J. subtriplinerve treatment groups. These results suggest that J. subtriplinerve, when used as tea or a functional food, is nontoxic and has clear chemopreventive effects against breast cancer.

Two New Steroidal Saponins with Potential Anti-Inflammatory Effects from the Aerial Parts of Gnetum formosum Markgr.

Gnetum formosum Markgr., a member of the Gnetaceae family, is distributed in Vietnam. This plant remains a botanical enigma with an unexplored diversity of chemical constituents and pharmacological effects. In this study, two new steroidal saponins, namely gnetumosides A (1) and B (2), were isolated from the aerial parts of G. formosum. Their chemical structures were elucidated using spectroscopic techniques, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and NMR, along with chemical hydrolysis and comparison with the reported literature. The potential anti-inflammatory effects of the isolated compounds were evaluated by measuring lipopolysaccharide-stimulated nitric oxide (NO) production in murine macrophage cells. Notably, compound 1 exhibited the most potent inhibitory activity (IC50 = 14.10 ± 0.75 µM), comparable to dexamethasone. Additionally, the mechanisms underlying the observed anti-inflammatory effects were investigated through molecular docking and molecular dynamics simulations on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. This study is the first to investigate the chemical constituents and pharmacological effects of G. formosum.

Two new eudesmane sesquiterpene glucosides from the aerial parts of Artemisia vulgaris.

Using combined chromatographic methods, two new sesquiterpene glucosides, vulgarosides A (1) and B (2), and two known analogs ainsliaside E (3) and pumilaside A (4) were isolated from the aerial parts of Artemisia vulgaris. Their chemical structures were established by spectroscopic methods, including one and two-dimensional nuclear magnetic resonance (1 D and 2 D-NMR) spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). In addition, their cytotoxicity on five human cancer cell lines, including KB (epidermoid carcinoma), HepG2 (hepatocarcinoma), MCF7 (breast carcinoma), SK-Mel-2 (melanoma), and LNCaP (prostate cancer) was also evaluated by the SRB assay. However, none of the tested eudesmane sesquiterpene glycosides showed significant cytotoxicity (IC50>100 µM).

A New Ceanothane-Type Triterpenoid Saponin Isolated from Gouania leptostachya DC. var. tonkinensis Pit. and Its Underlying Anti-Inflammatory Effects.

Metabolites from medicinal plants continue to hold significant value in the exploration and advancement of novel pharmaceuticals. In the search for plants containing compounds with anti-inflammatory effects, we observed that the ethanol (EtOH) extract obtained from the aerial components of Gouania leptostachya DC. var. tonkinensis Pit. exhibited substantial suppression of nitric oxide (NO) in vitro. In a phytochemical study on an EtOH extract of G. leptostachya, 11 compounds were purified, including one unreported compound namely gouanioside A (1). Their chemical structures were unambiguously determined through the use of various spectroscopic techniques, such as 1 and 2D NMR, IR, and HR-ESI-MS, and by producing derivatives via chemical reactions. The EtOH extract, fractions, and a new compound exerted inflammatory effects by altering NO synthesis in murine RAW264.7 macrophage cells stimulated with lipopolysaccharide. The underlying inflammatory mechanism of the new compound 1 was also explored through various in vitro experiments. The results of this study indicate the potential usefulness of new compound 1 from G. leptostachya as a treatment for inflammatory diseases.

Secondary metabolites from the fruit peels of Durio zibethinus L. and their cytotoxic activity.

Three new glucosides, ziberthinosides A-C (1-3), and six known compounds, cleomiscosins A-D (4-7), sporogen AO-2 (8) and sapinofuranone A (9), were isolated from a methanol extract of Durio zibethinus fruit peels. Their chemical structures were elucidated by analyses of their 1 D/2D NMR and HR-ESI-MS data as well as by comparison with the literature values. The absolute configuration of sporogen AO-2 (8) was confirmed by ECD calculation. Of the isolates, compounds 8 and 9 were cytotoxic toward all MCF7, HepG2 and SK-LU-1 cell lines, with IC50 values ranging from 10.7 to 34.9 µM. Our results contribute to better understanding of the chemical constituents of the high valued durian fruit and their pharmacological effect, such as cytotoxicity.