Kaempferide triggers apoptosis and paraptosis in pancreatic tumor cells by modulating the ROS production, SHP-1 expression, and the STAT3 pathway.

Pancreatic cancer is one of the deadliest diseases with a poor prognosis and a five-survival rate. The STAT3 pathway is hyperactivated which contributes to the sustained proliferative signals in pancreatic cancer cells. We have isolated kaempferide (KF), an O-methylated flavonol, from the green propolis of Mimosa tenuiflora and examined its effect on two forms of cell death namely, apoptosis and paraptosis. KF significantly increased the cleavage of caspase-3 and PARP. It also downmodulated the expression of Alix (an intracellular inhibitor of paraptosis) and increased the expression of CHOP and ATF4 (transcription factors that promote paraptosis) indicating that KF promotes apoptosis as well as paraptosis. KF also increased intracellular reactive oxygen species (ROS) suggesting the perturbance of the redox state. N-acetylcysteine reverted the apoptosis- and paraptosis-inducing effects of KF. Some ROS inducers are known to suppress the STAT3 pathway and investigation revealed that KF downmodulates STAT3 and its upstream kinases (JAK1, JAK2, and Src). Additionally, KF also elevated the expression of SHP-1, a tyrosine phosphatase which is involved in the negative modulation of the STAT3 pathway. Knockdown of SHP-1 prevented KF-driven STAT3 inhibition. Altogether, KF has been identified as a promoter of apoptosis and paraptosis in pancreatic cancer cells through the elevation of ROS generation and SHP-1 expression.

Identification of new anti-mycobacterial agents based on quinoline-isatin hybrids targeting enoyl acyl carrier protein reductase (InhA).

Tuberculosis (TB) is a global issue that poses a significant economic burden as a result of the ongoing emergence of drug-resistant strains. The urgent requirement for the development of novel antitubercular drugs can be addressed by targeting specific enzymes. One such enzyme, Mycobacterium tuberculosis (MTB) enoyl-acyl carrier protein (enoyl-ACP) reductase (InhA), plays a crucial role in the survival of the MTB bacterium. In this research study, a series of hybrid compounds combining quinolone and isatin were synthesized and assessed for their effectiveness against MTB, as well as their ability to inhibit the activity of the InhA enzyme in this bacterium. Among the compounds tested, 7a and 5g exhibited the most potent inhibitory activity against MTB, with minimum inhibitory concentration (MIC) values of 55 and 62.5 µg/mL, respectively. These compounds were further evaluated for their inhibitory effects on InhA and demonstrated significant activity compared to the reference drug Isoniazid (INH), with IC50 values of 0.35 ± 0.01 and 1.56 ± 0.06 µM, respectively. Molecular docking studies investigated the interactions between compounds 7a and 5g and the target enzyme, revealing hydrophobic contacts with important amino acid residues in the active site. To further confirm the stability of the complexes formed by 5g and 7a with the target enzyme, molecular dynamic simulations were employed, which demonstrated that both compounds 7a and 5g undergo minor structural changes and remain nearly stable throughout the simulated process, as assessed through RMSD, RMSF, and Rg values.

Vasorelaxant Activity of (2S)-Sakuranetin and Other Flavonoids Isolated from the Green Propolis of the Caatinga Mimosa tenuiflora.

Some in vitro and in vivo evidence is consistent with the cardiovascular beneficial activity of propolis. As the single actors responsible for this effect have never been identified, an in-depth investigation of flavonoids isolated from the green propolis of the Caatinga Mimosa tenuiflora was performed and their mechanism of action was described. A comprehensive electrophysiology, functional, and molecular docking approach was applied. Most flavanones and flavones were effective CaV1.2 channel blockers with a potency order of (2S)-sakuranetin > eriodictyol-7,3'-methyl ether > quercetin 3-methyl ether > 5,4'-dihydroxy-6,7-dimethoxyflavanone > santin > axillarin > penduletin > kumatakenin, ermanin and viscosine being weak or modest stimulators. Except for eriodictyol 5-O-methyl ether, all the flavonoids were also effective spasmolytic agents of vascular rings, kumatakenin and viscosine also showing an endothelium-dependent activity. (2S)-Sakuranetin also stimulated KCa1.1 channels both in single myocytes and vascular rings. In silico analysis provided interesting insights into the mode of action of (2S)-sakuranetin within both CaV1.2 and KCa1.1 channels. The green propolis of the Caatinga Mimosa tenuiflora is a valuable source of multi-target vasoactive flavonoids: this evidence reinforces its nutraceutical value in the cardiovascular disease prevention arena.

Essential Oils from the Leaves and Stem Barks of Pluchea indica (L.) Less.: Chemical Analysis, Cytotoxicity, Anti-inflammation, Antimicrobial Activity, Molecular Docking, and ADMET Profiling.

Pluchea indica (L.) Less. is a medicinal plant native to Asia. Traditionally, it is known for numerous traditional uses, such as treatments for fever, cough, and digestive issues. The present investigation aims to determine the chemical compositions of essential oils from its fresh leaves and stem barks. By using hydro-distillation and the GC-FID/MS (gas chromatography-flame ionization detection/mass spectrometry) analysis, the studied samples were dominated by sesquiterpene hydrocarbons (76.8-82.2%) and their oxygenated derivatives (8.4-19.0%). ß-Selinene (42.0-43.5%) and silphinene (21.1-22.9%) were the main compounds. Significantly, the stem bark essential oil strongly monitored the growth of four cancer cell lines K562, HeLa, HepG2, and MCF-7 with IC50 values of 2.89-7.34 µg/mL. Both studied samples showed strong anti-inflammatory activity against NO (nitric oxide) production with IC50 values of 21.81-23.18 µg/mL. The studied sample also exhibited antimicrobial activity at different levels. The molecular docking study revealed that ß-selinene exhibited the strongest binding affinity for all four cancer-related protein targets: epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), Abelson tyrosine-protein kinase 1 (ABL1), and phosphatidylinositol 3-kinase (PI3K-α). The ADMET profiles of the major compounds were also predicted to provide insights for further research considerations.

Chemical Compositions and Antimicrobial and Mosquito Larvicidal Activities of the Leaf Essential Oils of Goniothalamus yunnanensis W.T.Wang and G. touranensis Ast: Experimental and In Silico Approaches.

The current research describes a phytochemical analysis and antimicrobial activity of essential oils extracted from the leaves of two Vietnamese Annonaceae species Goniothalamus yunnanensis W.T.Wang and G. touranensis Ast. By the GC-FID/MS (gas chromatography-flame ionization detection/mass spectrometry) analyses, sesquiterpene hydrocarbons accounted for the highest percentage of 68.22% in G. yunnanensis leaf essential oil with bicyclogermacrene (31.03%) and (E)-caryophyllene (21.12%) being the main compounds. G. touranensis leaf essential oil was dominated by monoterpene hydrocarbons (57.08%) with p-cymene (19.95%) and α-pinene (16.82%) being the major compounds. Two oil samples showed strong antibacterial effects on the Gram-positive bacteria Enterococcus faecalis ATCC51299, Staphylococcus aureus ATCC29213, and Bacillus cereus ATCC11778 with the MIC values of 16-64 µg/mL. They also inhibited the growth of the yeast Candida albicans ATCC 60193 with the same MIC value of 128 µg/mL. Both two oil samples showed strong mosquito larvicidal activity against four-instar larvae of Aedes aegypti and Ae. albopictus with the 24-h LC50 values of 16.75-27.60 µg/mL and 24-h LC90 values of 24.31-46.18 µg/mL. Docking results indicated that bicyclogermacrene and p-cymene exhibited the highest ΔG (binding affinity) values of -8.208 and -6.799 kcal/mol with the olfactory binding proteins (OBPs) of Ae. aegypti and Ae. albopictus, respectively.

Health benefits of fraxetin: From chemistry to medicine.

Fraxetin is a bioactive molecule present in various natural plants, especially Cortex Fraxini. Evidenced outcomes in phytochemical and biological analyses for this agent are now available in the literature, but an insightful review is yet unknown. The goal of the current research is to offer a panoramic illustration of natural observation, biosynthesis, synthesis, pharmacology, and pharmacokinetics for fraxetin. Esculetin and ferulic acid acted as precursors in the enzymatic biosynthetic route, whereas fraxetin could be easily synthesized from simple phenols. A great deal of interest was obtained in using this molecule for pharmacological targets. Herein, its pharmacological value included anticancer, antioxidative, anti-inflammatory, antidiabetic, antiobesity, and antimicrobial activities, as well as the protection of the liver, neurons, heart, bone, lung, kidney, and others. Anticancer activity may involve the inhibition of proliferation, invasion, and migration, together with apoptotic induction. Health benefits from this molecule were deduced from its ability to suppress cytokines and protect the immune syndrome. Various signaling pathways, such as Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt), nuclear factor kappa B (NF-κB)/NLRP3, Akt/AMPK, have been proposed for in vitro and in vivo mechanisms of action. Fraxetin is highly distributed to rat plasma and several organs. However, more pharmacokinetic studies to improve its bioavailability are needed since its solubility in water is still limited.

Chemical Profile and Biological Activities of Fungal Strains Isolated from Piper nigrum Roots: Experimental and Computational Approaches.

The current report describes the chemical investigation and biological activity of extracts produced by three fungal strains Fusarium oxysporum, Penicillium simplicissimum, and Fusarium proliferatum isolated from the roots of Piper nigrum L. growing in Vietnam. These fungi were namely determined by morphological and DNA analyses. GC/MS identification revealed that the EtOAc extracts of these fungi were associated with the presence of saturated and unsaturated fatty acids. These EtOAc extracts showed cytotoxicity towards cancer cell lines HepG2, inhibited various microbacterial organisms, especially fungus Aspergillus niger and yeast Candida albicans (the MIC values of 50-100 µg/mL). In α-glucosidase inhibitory assay, they induced the IC50 values of 1.00-2.53 µg/mL were better than positive control acarbose (169.80 µg/mL). The EtOAc extract of F. oxysporum also showed strong anti-inflammatory activity against NO production and PGE-2 level. Four major compounds linoleic acid (37.346 %), oleic acid (27.520 %), palmitic acid (25.547 %), and stearic acid (7.030 %) from the EtOAc extract of F. oxysporum were selective in molecular docking study, by which linoleic and oleic acids showed higher binding affinity towards α-glucosidase than palmitic and stearic acids. In subsequent docking assay with inducible nitric oxide synthase (iNOS), palmitic acid, oleic acid and linoleic acid could be moderate inhibitors.

Essential Oils of Five Syzygium Species Growing Wild in Vietnam: Chemical Compositions and Antimicrobial and Mosquito Larvicidal Potentials.

The essential oils of five Vietnamese Syzygium species (Syzygium levinei, S. acuminatissimum, S. vestitum, S. cumini, and S. buxifolium) were first hydro-distilled and analyzed using GC-FID/MS (gas chromatography-flame ionization detection/mass spectrometry). Monoterpene hydrocarbons, sesquiterpene hydrocarbons, and oxygenated sesquiterpenoids were the main chemical classes in these oils. All these essential oils showed good-excellent antimicrobial activities against Gram-positive bacteria Enterococcus faecalis, Staphylococcus aureus, and Bacillus cereus, and the yeast Candida albicans. S. levinei leaf essential oil, rich in bicyclogermacrene (25.3%), (E)-ß-elemene (12.2%), (E)-caryophyllene (8.2%), and ß-selinene (7.4%), as well as S. acuminatissimum fruit essential oil containing (E)-caryophyllene (14.2%), α-pinene (12.1%), caryophyllene oxide (10.9%), ß-selinene (10.8%), α-selinene (8.0%), and α-humulene (5.7%), established the same MIC value of 8 µg/mL against E. faecalis and B. cereus, which were much better than the positive control streptomycin (MIC 128-256 µg/mL). The studied essential oils showed the potential to defend against mosquitoes since they caused the 24 and 48 h LC50 values of less than 50 µg/mL against the growth of Culex quinquefasciatus and Aedes aegypti larvae. Especially, S. buxifolium leaf essential oil strongly inhibited Ae. aegypti larvae with 24 and 48 h LC50 values of 6.73 and 6.73 µg/mL, respectively, and 24 and 48 h LC90 values of 13.37 and 10.83 µg/mL, respectively. These findings imply that Vietnamese Syzygium essential oils might have potential for use as supplemental antibacterial agents or as "green" alternatives for the control of mosquitoes.

Antioxidative and α-glucosidase inhibitory constituents of Polyscias guilfoylei: experimental and computational assessments.

Searching for bioactive agents from medicinal plants, eleven constituents were isolated from Polyscias guilfoylei stem for the first time, including a nucleoside uracil (1), two sterols ß-sitosterol (2) and daucosterol (3), a saponin androseptoside A (4), two lignans (+)-pinoresinol (5) and (+)-syringaresinol (6), four phenolic acids protocatechuic acid (7), methyl protocatechuate (8), caffeic acid (9), and 5-O-caffeoylquinic acid (10), and a flavonoid quercitrin (11). Metabolites 1, 4, and 6-11 have never been observed in genus Polyscias before. Phenolic compounds 7 and 9 possessed the respective IC50 values of 21.33 and 13.88 µg/mL in DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidative assay, as compared with that of the positive control resveratrol (IC50 = 13.21 µg/mL). From density functional theory (DFT) calculated approach, the DPPH free radical scavenging capacity of two compounds 7 and 9 can be explained by the role of OH groups at carbons C-3 and C-4. Antioxidative actions of these two potential agents are followed HAT (H atom transfer) mechanism by OH bond disruption in gas, but SPLET (sequential proton loss electron transfer) mechanism in solvents water and methanol. Compared to 4-OH group, 3-OH group showed better bond disruption enthalpies and better kinetic energies since it reacted with HOO• and DPPH radicals. Sterols 2-3 and flavonoid 11 induced the IC50 values of < 2.0 µg/mL better than the positive control acarbose (IC50 = 184.0 µg/mL) in α-glucosidase inhibitory assay. Their interactions with human intestinal C- and N-terminal domains of α-glucosidase were explored using molecular docking study. The obtained results proved that compounds 2, 3, and 11 bind relatively stronger with the C-terminal domain than to the N-terminal domain through pivotal residues in the binding site and could be hypothesized as mixed inhibitors.

Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators.

Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of targeting KCa1.1 and CaV1.2 channels, the expression of which is altered in hypertension, the in vitro vascular effects of a series of flavonoids extracted from the heartwoods, roots, and leaves of Dalbergia tonkinensis Prain, widely used in traditional medicine, were assessed. Rat aorta rings, tail artery myocytes, and docking and molecular dynamics simulations were used to analyse their effect on these channels. Formononetin, orobol, pinocembrin, and biochanin A showed a marked myorelaxant activity, particularly in rings stimulated by moderate rather than high KCl concentrations. Ba2+ currents through CaV1.2 channels (IBa1.2) were blocked in a concentration-dependent manner by sativanone, 3'-O-methylviolanone, pinocembrin, and biochanin A, while it was stimulated by ambocin. Sativanone, dalsissooside, and eriodictyol inhibited, while tectorigenin 7-O-[ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside], ambocin, butin, and biochanin A increased IKCa1.1. In silico analyses showed that biochanin A, sativanone, and pinocembrin bound with high affinity in target-sensing regions of both channels, providing insight into their potential mechanism of action. In conclusion, Dalbergia tonkinensis is a valuable source of mono- and bifunctional, vasoactive scaffolds for the development of novel antihypertensive drugs.

Vasorelaxing Activity of R-(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol from Dalbergia tonkinensis: Involvement of Smooth Muscle CaV1.2 Channels.

Dalbergia species heartwood, widely used in traditional medicine to treat various cardiovascular diseases, might represent a rich source of vasoactive agents. In Vietnam, Dalbergia tonkinensis is an endemic tree. Therefore, the aim of the present work was to investigate the vascular activity of R-(-)-3'-hydroxy-2,4,5-trimethoxydalbergiquinol isolated from the heartwood of D. tonkinensis and to provide circular dichroism features of its R absolute configuration. The vascular effects of R-(-)-3'-hydroxy-2,4,5-trimethoxydalbergiquinol were assessed on the in vitro mechanical activity of rat aorta rings, under isometric conditions, and on whole-cell Ba2+ currents through CaV1.2 channels (IBa1.2) recorded in single, rat tail main artery myocytes by means of the patch-clamp technique. R-(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol showed concentration-dependent, vasorelaxant activity on both endothelium-deprived and endothelium intact rings precontracted with the α 1 receptor agonist phenylephrine. Neither the NO (nitric oxide) synthase inhibitor Nω-nitro-L-arginine methyl ester nor the cyclooxygenase inhibitor indomethacin affected its spasmolytic activity. R-(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol-induced vasorelaxation was antagonized by (S)-(-)-Bay K 8644 and unaffected by tetraethylammonium plus glibenclamide. In patch-clamp experiments, R-(-)-3'-hydroxy-2,4,5-trimethoxydalbergiquinol inhibited IBa1.2 in a concentration-dependent manner and significantly decreased the time constant of current inactivation. R-(-)-3'-Hydroxy-2,4,5-trimethoxydalbergiquinol likely stabilized the channel in its closed state, as suggested by molecular modelling and docking simulation to the CaV1.2 channel α 1c subunit. In conclusion, D. tonkinensis species may represent a source of agents potentially useful for the development of novel antihypertensive drugs.

Morinlongosides A-C, Two New Naphthalene Glycoside and a New Iridoid Glycoside from the Roots of Morinda longissima.

Two new naphthalene glycosides, morinlongosides A and B (1, 2) and a new iridoid glycoside, morinlongoside C (3), together with four known ones, geniposidic acid (4), (3R)-3-O-[ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranosyl]-l-octen-3-ol (5), lucidin-3-O-ß-primeveroside (6), and morindone-6-O-ß-gentiobioside (7), were isolated from the roots of Morinda longissima Y. Z. RUAN. The structures of all isolated compounds (1-7) were elucidated on the basis of spectroscopic data (high resolution (HR)-MS, one and two dimensional (1/2D)-NMR).

In vitro vasoactivity of zerumbone from Zingiber zerumbet.

The sesquiterpene zerumbone, isolated from the rhizome of Zingiber zerumbet Sm., besides its widespread use as a food flavouring and appetiser, is also recommended in traditional medicine for the treatment of several ailments. It has attracted great attention recently for its effective chemopreventive and therapeutic effects observed in various models of cancer. To assess the zerumbone safety profile, a pharmacology study designed to flag any potential adverse effect on vasculature was performed. Zerumbone was tested for vasorelaxing activity on rat aorta rings and for L-type Ba(2+) current blocking activity on single myocytes isolated from the rat-tail artery. The spasmolytic effect of zerumbone was more marked on rings stimulated with 60 mM than with 30 mM K(+) (IC50 values of 16 µM and 102 µM, respectively). In the presence of 60 mM K(+), zerumbone concentration-dependently inhibited the contraction induced by the cumulative additions of Ca(2+), this inhibition being inversely related to the Ca(2+) concentration. Phenylephrine-induced contraction was inhibited by the drug, though less efficiently and independently of the presence of an intact endothelium, without affecting Ca(2+) release from the intracellular stores. Zerumbone inhibited the L-type Ba(2+) current (estimated IC50 value of 458.7 µM) and accelerated the kinetics of current decay. In conclusion, zerumbone showed an overall weak in vitro vasodilating activity, partly attributable to the blocking of the L-type Ca(2+) channel, which does not seem to represent, however, a serious threat to its widespread use.

Paratrimerins A and B, Two New Dimeric Monoterpene-Linked Coumarin Glycosides from the Roots and Stems of Paramignya trimera.

Two new dimeric monoterpene-linked coumarin glucosides, paratrimerins A (1) and B (2), and three known coumarins, 6-(6-hydroxy-3,7-dimethylocta-2,7-dienyl)-7-hydroxycoumarin (3), ostruthin (4), and ninhvanin (5), were isolated from the roots and stems of Paramignya trimera (OLIV.) GUILL. collected in Khanh Hoa province, Vietnam. Compound 1 comprises two 7-O-ß-D-glucopyranoside coumarins linked at positions 6,6' via a 1,3,4,4-tetrasubstituted cyclohexene containing a monoterpene bridge, whereas compound 2 is a ß-D-apiofuranosyl(1→6)-ß-D-glucopyranosyl derivative of 1. The chemical structures of these compounds were determined by one dimensional (1D) and 2D-NMR and high resolution-electrospray ionization (HR-ESI)-MS spectroscopy.

The genus Myrsine: A review of phytochemistry, pharmacology, and toxicology.

BACKGROUND: Myrsine (the family Primulaceae) contains flowering species. Pharmacologically, the plants of this genus belong to a list of medicinal plants that induce infectious and inflammatory treatments. There are no scientific publications that review phytochemistry and pharmacological activities. OBJECTIVE: The compilation and classification of phytochemicals, chromatographic information, essential oils, and pharmacological reviews are the ultimate aim. METHODS: References on phytochemical and pharmacological investigations of Myrsine species were collected from various sources, such as Google Scholar, PubMed, and Web of Science from the 1990s to present. The main keyword "Myrsine" was used alone or in combination with others to search for references. RESULTS: Chromatographic procedure of Myrsine extracts led to the purification of 134 compounds. Flavonoids, mono-phenols, saponins, quinones, megastigmanes, and lignans were the main phytochemical classes. Myrsine Volatile compounds are monoterpenoids, sesquiterpenoids, and aliphatic compounds. Myrsine constituents established a widespread panel of pharmacological activities, such as cytotoxicity, antioxidant, antimicrobial, anti-parasite, tyrosine inhibition, and hepatoprotection, especially anti-inflammation. Novel flavonoids myrsininones A-B are better than the standard triclosan against bacteria Staphylococcus warneri, S. mutan, S. sanguis, and Actinomyces naeslundii. M. seguinii aerial part ethanolic extract inhibited LPS (lipopolysaccharide)-stimulated inflammatory Raw 264.7 cells via Src/Syk/NF-κB (sarcoma kinase/spleen tyrosine kinase/ nuclear factor-kappa B) and IRAK-1/AP-1 (interleukin-1 receptor-associated kinase-1/activating protein-1) signaling inhibition. Generally, Myrsine plant extracts showed no toxicity. CONCLUSION: Myrsine constituents are good antimicrobial, antioxidative, and anti-inflammatory agents. However, the majority of earlier research focuses on the pharmacological analyses of M. africana. Thus, comprehensive findings for the remaining species are needed.

The quassinoids bruceines A-M: pharmacology, mechanism of action, synthetic advance, and pharmacokinetics-a review.

Bruceines A-L are among the quassinoid representatives found in the medicinal plant Brucea javanica (L.). An overview of their pharmacological activities is still unknown. The given research deals with highlights in their pharmacological result, molecular mechanism of action, synthetic progress, and pharmacokinetics. From previous evidence, bruceine derivatives are potential agents for anticancer treatments, as well as they are appropriate to treat inflammation, diabetes, and parasitic infections, and protect the neurons, kidneys, and lungs. Cytokine inhibitions, oxidative stress responses, and various signaling pathways, such as MAPK (mitogen-activated protein kinase) and NF-κB (nuclear factor-kappa B), have been proposed as the underlying mechanisms of action. Synthetic approaches to synthesize new derivatives with enhancement activities are based on free hydroxyl group modifications. Bruceines seem to be promptly absorbed by both oral and intravenous administrations, but their bioavailability is not high (less than 6%). Pre-clinical and clinical studies to prove their anticancer potential and other activities are urgent. Structural modifications, nano-combinations, and synergistic effects are necessary.

The Mushroom Albatrellus confluens: A Minireview on Phytochemistry, Biosynthesis, Synthesis and Pharmacological Activities.

BACKGROUND: Albatrellus confluens is one of the representative species in the Polyporaceae family. Its major mero terpenoid grifolin and related compounds have the potential for drug applications. OBJECTIVE: The current study aims to briefly provide an insightful view of the phytochemistry, biosynthesis, synthesis, and pharmacology of A. confluens metabolites. METHODS: Data collection was performed using electronic resources, e.g., Google Scholar, PubMed, and Sci-Finder from the 1990s to the present, while Albatrellus confluens is the most meaningful keyword in the search for publications. The Latin name Albatrellus confluens (Alb. & Schwein.) Kotl. & Pouzar is in accordance with the name listing on www.mycobank.org. RESULTS: By chromatography column procedures, it indicated that A. confluens species was associated with the presence of 57 secondary metabolites, in which nitrogenous compounds, meroterpenoids, polyene pyrones, and polyesters can be seen as the main phytochemical classes. L-isoleucine was the parent molecule in biosynthetic and synthetic steps of A. confluens nitrogenous compounds. Numerous experiments revealed that A. confluens isolated compounds have a variety of pharmacological activities, such as anticancer, anti-inflammatory, vasorelaxant, and neuroprotective and skin whitening activities. Some isolates become potential cancer inhibitors. Grifolin induced apoptosis and promoted cell cycle arrest in A2780 ovarian cancer cells via the inactivation of the ERK1/2/Akt signaling pathway. Grifolic acid caused osteosarcoma cancer cell deaths by inhibiting NADH generation and ATP production without obvious toxicity. Neoalbaconol caused apoptosis and necroptosis in mice bearing nasopharyngeal C666-1 cancer cells via PDK1-PI3K/Akt signaling inhibition. CONCLUSION: The continuation of chromatographic separation and biomedical research is expected. Modern biological assays for explaining the pharmacological values of A. confluens constituents are warranted. Toxicological and pharmacokinetic assessments are urgently needed.

Scutellarein: a review of chemistry and pharmacology.

OBJECTIVES: To get a better understanding of the scientific values of flavone scutellarein (SCT), and to encourage its applications in human health, the current review systematically summarizes the natural observation, biosynthesis, synthesis, pharmacology, pharmacokinetics, and recent synthetic advances. KEY FINDINGS: Scientific sources to search for references included Google Scholar, Scopus, Web of Science, PubMed, Sci-Finder, and journal websites. The references have been collected from the 1970s to the present. "Scutellarein" is the most meaningful keyword to search for publications, in which it was used alone or in combination with other keywords. SUMMARYS: SCT as a hydrophobic flavonoid can be found in various medicinal plants of the families Lamiaceae, Compositae, and Verbenaceae. Flavone SCT has drawn much interest due to its wide pharmacological effects, such as anticancer, anti-inflammation, antioxidant, antiobesity, and vasorelaxant. The SCT treatments also possessed a lot of positive results in the neuron, liver, heart, lung, kidney, bone, and skin protective experiments, and human sperm function enhancement. Its underlying mechanism of action may relate to the apoptotic program and cytokine inhibition by regulating a panel of the signaling pathway, e.g., NF-κB (nuclear factor kappa B)/MAPK (mitogen-activated protein kinase), IκBa (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitors alpha)/NF-κB, TRAF2 (tumor necrosis factor receptor-associated factor 2)/NF-κB, and PTEN (phosphatase and tension homologue deleted on chromosome 10)/Akt (protein kinase B)/NF-κB. In addition, the metabolic actions and synthetic derivative promotions of SCT were mostly based on the substitution of hydroxyl groups. Collectively, the studies that aim to highlight the role of scutellarein in preclinical and clinical treatments are urgently needed. More and more experiments to improve its bioavailability are expected.

3,3'-O-dimethylquercetin: A bi-functional vasodilator isolated from green propolis of the Caatinga Mimosa tenuiflora.

In the search for novel, bi-functional compounds acting as CaV1.2 channel blockers and K+ channel stimulators, which represent an effective therapy for hypertension, 3,3'-O-dimethylquercetin was isolated for the first time from Brazilian Caatinga green propolis. Its effects were investigated through electrophysiological, functional, and computational approaches. In rat tail artery myocytes, 3,3'-O-dimethylquercetin blocked Ba2+ currents through CaV1.2 channels (IBa1.2) in a concentration-dependent manner, with the inhibition being reversed upon washout. The compound also shifted the voltage dependence of the steady-state inactivation curve to more negative potentials without affecting the slope of the inactivation and activation curves. Furthermore, the flavonoid stimulated KCa1.1 channel currents (IKCa1.1). In silico simulations provided additional evidence for the binding of 3,3'-O-dimethylquercetin to KCa1.1 and CaV1.2 channels and elucidated its mechanism of action. In depolarized rat tail artery rings, the flavonoid induced a concentration-dependent relaxation. Moreover, in rat aorta rings its antispasmodic effect was inversely related to the transmembrane K+ gradient. In conclusion, 3,3'-O-dimethylquercetin demonstrates effective in vitro vasodilatory properties, encouraging the exploration of its scaffold to develop novel derivatives for potential use in the treatment of hypertension.

New nor-lignans from the leaves of styrax annamensis guillaumin.

Phytochemical study of the leaves of Styrax annamensis Guillaumin resulted in the isolation of a new natural product egonol-3''-sulphate (1), and two new derivatives egonol-3-methyl-D-galactopyranoside (2) and 7-methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran-5-carboxamide (3). Their chemical structures were -elucidated by spectroscopic data. Compounds 1 and 3 significantly established a great role for the chemotaxonomic aspect. Compound 1 showed cytotoxicity against four cancer cell lines KB, HepG2, Lu, and MCF7 with the IC50 values of 84.90-101.69 µg/mL, and exhibited acetylcholinesterase (AChE) inhibitory activity with the IC50 value of 97.08 µg/mL.