(±)-Salvicatone A: A Pair of C27-Meroterpenoid Enantiomers with Skeletons from the Roots and Rhizomes of Salvia castanea Diels f. tomentosa Stib.

(±)-Salvicatone A (1), a C27-meroterpenoid featuring a unique 6/6/6/6/6-pentacyclic carbon skeleton with a 7,8,8a,9,10,10a-hexahydropyren-1 (6H)-one motif, was isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Its structure was characterized by comprehensive spectroscopic analyses along with computer-assisted structure elucidation, including ACD/structure elucidator and quantum chemical calculations with 1H/13C NMR and electronic circular dichroism. Biogenetically, compound 1 was constructed from decarboxylation following [4 + 2] Diels-Alder cycloaddition reaction between caffeic acid and miltirone analogue. Bioassays showed that (-)-1 and (+)-1 inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophage cells with an IC50 value of 6.48 ± 1.25 and 15.76 ± 5.55 µM, respectively. The structure-based virtual screening based on the pharmacophores in ePharmaLib, as well as the molecular docking and molecular dynamics simulations study, implied that (-)-1 and (+)-1 may potentially bind to retinoic acid receptor-related orphan receptor C to exert anti-inflammatory activities.

A novel ent-pimarane-type diterpenoid from Sigesbeckia glabrescens with anti-inflammatory activity.

A novel ent-pimarane-type diterpenoid, sigesbeckia J (1), along with two known diterpenoids, siegesbeckia acid (2) and ent-18-acetoxy-16R,17-dihydroxykauran-19-oic acid (3), were isolated from the aerial parts of Sigesbeckia glabrescens Makino. Their chemical structures were elucidated based on extensive spectroscopic interpretation. The absolute configuration of ent-pimarane-type diterpenoid (1) was determined by comparing experimental and calculated ECD spectra. Compared with the positive control minocycline (IC50 32.84 µM), compound 1 exhibited moderate cell growth anti-inflammatory activities in vitro by testing their inhibition of LPS-induced NO production in BV2 microglial cells, with IC50 value of 58.74 µM.

Two novel polyketones from the leaves and twigs of Clerodendrum trichotomum.

Two novel polyketones, along with four known compounds, were isolated from the leaves and twigs of Clerodendrum trichotomum. Their structures were determined to be clerodendruketone A (1), clerodendruketone B (2), ecdysanols E (3), ecdysanols D (4), 5,5'-dimethoxy-7-oxolariciresinol (5), and (-)-(7'S,8S,8'R)-4,4'-dihydroxy-3,3',5,5'-tetramethoxy-7',9-epoxy-lignan-9'-ol-7-one (6) through the methods of NMR, HRESIMS and ECD data analyses. The antioxidant effects against free radical were tested by DPPH assay. The antibacterial activity against Escherichia coli and Staphylococcus aureus were tested by turbidimetry assay. The results demonstrated that compounds 1 and 2 had significative antibacterial activity, and compound 3 had moderate antioxidant activity.

[A new norsesquiterpenoid from Schisandra chinensis].

This study investigated the chemical components from the leaves and stems of Schisandra chinensis. Three norsesquiterpenoids were isolated from S. chinensis by various column chromatographies(silica gel, Sephadex LH-20, and MCI), reversed-phase medium-pressure preparative, and semi-preparative high-performance liquid chromatography(HPLC). Their structures were identified based on physicochemical properties, mass spectrometry(MS), nuclear magnetic resonance(NMR), ultraviolet(UV), and electro-nic circular dichroism(ECD) as(3R,4R,5R,6S,7E)-3,4,5,6-tetrahydroxy-7-megastigmen-9-one(1),(3S,5R,6R,7E)-3,5,6-trihydroxy-7-megastigmen-9-one(2), and(3S,4R,9R)-3,4,9-trihydroxymegastigman-5-ene(3). Compound 1 was a new compound, and its absolute configuration was determined by ECD. Compounds 2 and 3 were isolated from the Schisandra plant for the first time.

Sesquiterpene Lactones from Sigesbeckia glabrescens Possessing Potent Anti-inflammatory Activity by Directly Binding to IKKα/ß.

Chromatographic fractionation of Sigesbeckia glabrescens led to the identification of 10 new sesquiterpene lactones, named siegesbeckialides I-O (1-7) and glabrescones A-C (8-10), along with 14 known analogues. An anti-inflammatory activity assay showed that siegesbeckialide I (1) most potently inhibited LPS-induced NO production in RAW264.7 murine macrophages. Furthermore, siegesbeckialide I suppressed the protein expression of iNOS and COX2, as well as the release of PGE2, IL-1ß, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells. Mechanistically, siegesbeckialide I directly binds to inhibitors of IKKα/ß and suppresses their phosphorylation. This leads to the inhibition of IKKα/ß-mediated phosphorylation and degradation of inhibitor α of NF-κB (IκBα), as well as the activation of NF-κB signaling.

Euphorfistrines A-G, cytotoxic and AChE inhibiting triterpenoids from the roots of Euphorbia fischeriana.

Seven new triterpenoids including two cycloartanes (1-2), a lanostane (3), a tirucallane (4), a dammarane (5), an ursane (6), and an oleanane (7), along with nineteen known triterpenoids (8-26), have been obtained from the roots of Euphorbia fischeriana. Their structures were established by NMR, HRESIMS, single-crystal X-ray diffraction analysis, Mosher's method, NMR calculations, ECD analysis, and comparison with structurally related known analogues. Among them, compounds 1 and 8 were a pair of cycloartane-type triterpenoids epimers. Our bioassays have established that compounds 1-5 and 10 displayed moderate cytotoxic effects, and the structure-activity relationships of cycloartane-type triterpenoids (CTTs) were further examined. Notably, some triterpenoids displayed moderate inhibitory effects against AChE by an in vitro screened experiment. Triterpenoid 7 (Euphorfistrine G, ETG) displayed the potent inhibitory effect with IC50 = 2.45 and Ki = 2.30 µM (inhibition kinetic). And, in silico docking analyses have been performed to investigate the inhibitory mechanism of compound 7.

ent-Pimarane diterpenoids from Siegesbeckia glabrescens with anti-inflammatory activity.

Nine new ent-pimarane-type diterpenoids, siegesbeckia A-I (1-9), together with four known analogues ent-3α,15,16,19-tetrahydroxypimar-8(14)-ene (10), 15,16-dihydroxypimar-8(14)-en-3-one (11), 14ß,16-epoxy-7-pimarene-3α,15ß-diol (12) and darutigenol (13), were obtained from the aerial parts of Siegesbeckia glabrescens Makino. The structures of these compounds were elucidated by the interpretation of HRESIMS, 1D NMR and 2D NMR data. Their configurations were determined by ECD analysis and the structure of compound 1 was confirmed by X-ray crystallography. Putative biosynthetic pathways were proposed for 1-13. The anti-inflammatory effects of the compounds were evaluated by testing their inhibition of LPS-induced NO production in BV2 microglial cells. The results revealed that new compounds 2, 6 and 8 exhibited potent inhibitory activities with IC50 values of 33.07, 42.39 and 63.26 µM, which compared well with the positive control minocycline (IC50 32.84 µM).

Two new alcohol glycosides from the roots of Paeonia intermedia C. A. Meyer.

Two new alcohol glycosides, 1-O-ß-d-glucopyranosyl-deoxypaeonisuffrone (1) and 9-O-ß-d-apiofuranoyl-(1→6)-ß-d-glucopyranosyl-xanthoarnol (2), together with eight known compounds (3-10), have been isolated from the dried roots of Paeonia intermedia C. A. Meyer. Their structures were mainly elucidated on the basis of ESIMS, one- and two-dimensional NMR techniques. Antibacterial activities of compounds 1-10 were evaluated, and compounds 9 and 10 showed antibacterial activities against Staphylococcus argenteus CMCC26003 and Escherichia coli CMCC44103. [Formula: see text].

Effects of Deacidification on Composition of Schisandra chinensis Ethanolic Extract and Studies on Acute Toxicity in Mice.

Schisandra chinensis Fructus (SCF), a well-known traditional medicinal material, is a rich source of dibenzocyclooctene type lignans and polyphenols, which are important ingredients in SCF and show various activities. SCF also contains about 18% organic acids, mainly citric acid, which makes the fruit and extract taste extremely sour and limited its application in beverages or food industries. In the present study, a chemical deacidification method was applied to defatted and non-defatted ethanol extract of SCF, and the effects on organic acid, lignans, and phenolic compounds were evaluated. Free radical scavenging activity and acute toxicity in mice before and after deacidification were also compared. Our results demonstrated that chemical deacidification significantly decreased the contents of organic acid and lignan compounds and markedly improves the safety of the ethanol extract of SCF, which will facilitate the comprehensive utilization of SCF extract in food and beverage industries.

Comparative Studies on Polysaccharides, Triterpenoids, and Essential Oil from Fermented Mycelia and Cultivated Sclerotium of a Medicinal and Edible Mushroom, Poria Cocos.

Poria cocos, an important medicinal and edible fungus, is well known in East Asia. The main active components are water-soluble polysaccharides (WPS) and triterpenoids. Due to the growing market demand, long cultivation period, and consumption of pine trunk during cultivation, alternative methods for producing P. cocos or its active components should be investigated. In this study, WPS, triterpenoids, monosaccharide composition, and essential oil in fermented mycelia and cultivated sclerotium were analyzed using UV spectrophotometry, HPLC, pre-column derivatization, and HS-GC/MS, respectively. Our results showed that the WPS and triterpenoids in mycelia are several times higher than those in sclerotium. Among the 62 compounds identified by HS-GC/MS analysis from the essential oil obtained from the fermentation media and a fresh external layer, the two main fragrances in common were linalool and methyl phenylacetate. Our results suggested that it is applicable to produce polysaccharides and triterpenoids by the fermentation of P. cocos, and a strategy to improve triterpenoid production in the fermentation process was proposed.

Constituents from the Seeds of Sophora Alopecuroides L.

Three new isoflavone glucosides, kudonol A-C (1-3), two new ester derivatives of phenylpropanoid, kudolignan A and B (4-5) and five known compounds, (-)-maackiain (6), neoliquiritin (7), methyl 4-coumarate (8), methyl ferulate (9) and (+)-wikstromol (10), were isolated from an extract of dried seeds of the traditional Chinese medicinal plant Sophora alopecuroides L. Their structures were established by NMR and HRESIMS data analyses. The monosaccharide part's configuration of isoflavone glucosides was confirmed by acid hydrolysis and analyzed by a JAsco OR-4090 chiral detector, comparing it to standard substance D-glucose. The cytotoxicity effects against HeLa, Hep3B, MCF-7 and H1299 cells were tested by CCK-8 assay.

Paris saponin VII induces cell cycle arrest and apoptosis by regulating Akt/MAPK pathway and inhibition of P-glycoprotein in K562/ADR cells.

Paris saponinVII (PSVII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. We found that PSVII could inhibit the growth of adriamycin-resistant human leukemia cells (K562/ADR) in a dose-dependent manner. Furthermore, the molecular mechanism underlying the cytotoxicity and downregulation of P-glycoprotein (P-gp) expression by PSVII was clarified. PSVII significantly suppressed cell proliferation by cell cycle arrest in the G0/G1 phase, which was associated with an obvious decrease in cyclin B1/D1 and CDK2/4/6 protein expression. Moreover, PSVII could attenuate mitochondrial membrane potential, increase the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decrease the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. We also found that JNK, ERK1/2, and p38 were regulated by PSVII in K562/ADR cells. And further studies indicated that the decrease in the reactive oxygen species level inhibited intrinsic P-gp expression. Therefore, PSVII-induced apoptosis in K562/ADR cells was associated with Akt/MAPK and the inhibition of P-gp. In addition, PSVII induced a robust autophagy in K562/ADR cells as demonstrated by the degradation of LC3-I. These results provide a biochemical basis for possible clinical applications of PSVII in the treatment of leukemia.

Chemical characteristics of the fungus Ganoderma lucidum and their inhibitory effects on acetylcholinesterase.

The chemical characteristic of a well-known folk medicine Ganoderma lucidum has been investigated by a series of chromatographic technologies, which displayed the presences of 45 lanostane type triterpenoids, including two new nor-lanostane triterpenoids (40, 41). Their structures were identified on the basis of spectroscopic data analysis (UV, IR, HRESIMS, 1D, and 2D NMR). Notably, some triterpenoids displayed moderate inhibitory effects against AChE (acetylcholinesterase) by an in vitro screened experiment. Triterpenoid 2 displayed the potent inhibitory effect with IC50 10.8 and Ki 14.95 µM (inhibition kinetic). The preliminary SAR has been discussed by the docking analyses between ganoderic acids (1, 2) and AChE.

[Phenolic acid derivatives of Euphorbia ebracteolata].

A variety of chromatographic methods were applied to research the chemical composition of the roots of Euphorbia ebracteolata. Meanwhile, the structures of these compounds were identified by spectroscopic data, such as 1D, 2D NMR and HR-ESI-MS. In the present research, a new phenolic acid compound, 1,3,4,5-tetrahydroxy-2-O-ß-D-[(6'-Gallic acyl)-glucopyranyl] isopentane(1), was isolated from the roots of E. ebracteolata, as well as three known compounds, isopropyl-2-O-ß-D-(6'-gallic acyl)-glucopyranoside(2), ellagic acid(3) and 3,4'-di-O-methylellagic acid(4) respectively. Additionally, compounds 2 and 4 were isolated from the Euphorbia genus for the first time.

Diterpenoid glucosides with anti-inflammatory activity from Sigesbeckia glabrescens.

Six previously undescribed diterpenoid glucosides, along with four known compounds, were isolated from the aerial parts of Sigesbeckia glabrescens. The structures and absolute configurations of undescribed compounds were elucidated using extensive spectroscopic techniques, ECD calculations and chemical methods. Compounds 1 and 8 exhibited anti-inflammatory activity against LPS-induced NO production in RAW 264.7 macrophages, with compound 8 demonstrating significant inhibitory activity compared to positive control minocycline, boasting an IC50 value at 14.20 µM.

From pill to pain: Alendronate-induced esophageal injury-A case report and review.

Background: Alendronate is used to treat Paget's bone disease, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis because it suppresses osteoclast activity to stop bone resorption. Case report: We present an exceptional case of esophagitis caused by alendronate. Blood tests and other data were normal when the patient was taken to the hospital, but an endoscopic examination revealed significant esophageal redness, erosion, and ulceration, along with pseudomembrane. The patient was given medicine after receiving a diagnosis of alendronate pill-induced esophagitis based on the pathological findings. Conclusion: This case report is a timely reminder of the importance of thorough pharmacovigilance, patient education, and smart therapeutic decision-making in the context of alendronate use. To properly treat and prevent problems with the esophagus caused by alendronate, additional research is required.

Targeting cyclin-dependent kinases: From pocket specificity to drug selectivity.

The development of selective modulators of cyclin-dependent kinases (CDKs), a kinase family with numerous members and functional variations, is a significant preclinical challenge. Recent advancements in crystallography have revealed subtle differences in the highly conserved CDK pockets. Exploiting these differences has proven to be an effective strategy for achieving excellent drug selectivity. While previous reports briefly discussed the structural features that lead to selectivity in individual CDK members, attaining inhibitor selectivity requires consideration of not only the specific structures of the target CDK but also the features of off-target members. In this review, we summarize the structure-activity relationships (SARs) that influence selectivity in CDK drug development and analyze the pocket features that lead to selectivity using molecular-protein binding models. In addition, in recent years, novel CDK modulators have been developed, providing more avenues for achieving selectivity. These cases were also included. We hope that these efforts will assist in the development of novel CDK drugs.

Two undescribed constituents from Salvia castanea Diels and evaluation of their cytotoxic activity.

One previously undescribed abietane diterpene alkaloid containing an oxazole ring (1), one unreported abietane diterpene (2), and nine known abietane diterpenes (3-11) were isolated from the roots and rhizomes of Salvia castanea Diels. Their structures and absolute configurations were elucidated by a combination of HRESIMS, 1D and 2D NMR, and ECD. All compounds were evaluated for their cytotoxic activity against several human cancer cell lines (HepG2, A549, H460, MCF7, PC3, and Hela). The results showed that 1 exhibited a moderate cytotoxic effect on HepG2 cells (IC50: 14.22 ± 1.05 µM) and was able to inhibit the cell growth of MCF7 and Hela cells by 35.08% and 47.26% respectively, at a concentration of 20 µM, while other compounds showed low cytotoxic activity.

Salvirrane A-F, six undescribed nordrimane sesquiterpene derivatives from Salvia castanea Diels f. tomentosa Stib and their cytotoxic activities.

Six undescribed nordrimane sesquiterpene derivatives, salvirrane A-F (1-6), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Comprehensive spectral analysis and a quantum chemical calculation strategy were employed to determine their structures. These compounds represent four previously unreported nordrimane carbon skeletal types in Salvia genus, including 15-nor-drimane, 11,15-di-nor-drimane, 14,15-di-nor-drimane, and 11,14,15-tri-nor-drimane sesquiterpenes. All compounds were evaluated for their cytotoxic activities against several human cancer cell lines (A549, H460, Hep3B, MCF7, PC3, and HeLa). The results showed that 3 exhibited low activity against MCF7 cells (IC50,72.72 ± 6.95 µM) and moderate activity against HeLa cells (IC50, 9.80 ± 0.64 µM). Moreover, the EdU (5-ethynyl-2'-deoxyuridine) assay demonstrates that 3 displays dose-dependent efficacy in suppressing the proliferation of HeLa cells. Network pharmacology and molecular docking technology implied that 3 may potentially bind to Src (proto-oncogene tyrosine-protein kinase) to exert anti-proliferative activity.

Natural Prenylflavonoids from Sophora flavescens Root Bark against Multidrug-Resistant Methicillin-Sensitive Staphylococcus aureus Targeting the Membrane Permeability.

The overuse of antibiotics in animal farming and aquaculture has led to multidrug-resistant methicillin-sensitive Staphylococcus aureus (MR-MSSA) becoming a common pathogen in foodborne diseases. Sophora flavescens Ait. serves as a traditional plant antibacterial agent and functional food ingredient. A total of 30 compounds (1-30) were isolated from the root bark of S. flavescens, consisting of 20 new compounds (1-20). In the biological activity assay, compound 1 demonstrated a remarkable inhibitory effect on MR-MSSA, with an MIC of 2 µg/mL. Furthermore, 1 was found to rapidly eliminate bacteria, inhibit biofilm growth, and exhibit exceptionally low cytotoxicity. Mechanistic studies have revealed that 1 possesses an enhanced membrane-targeting ability, binding to the bacterial cell membrane components phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and cardiolipin (CL). This disruption of bacterial cell membrane integrity increases intracellular reactive oxygen species, protein and DNA leakage, reduced bacterial metabolism, and ultimately bacterial death. In summary, these findings suggest that compound 1 holds promise as a lead compound against MR-MSSA.