New polycyclic polyprenylated acylphloroglucinols with antidepressant activities from Hypericum perforatum L.

Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperidiones A-F (1-6), were obtained from Hypericum perforatum L. Their structures were characterized via extensive spectroscopic analyses, the circular dichroism data of the in situ formed [Mo2(OCOCH3)4] complexes, the nuclear magnetic resonance calculation with DP4 + probability analysis, and the calculated electronic circular dichroism (ECD) spectra. Compounds 1-6 are bicyclic polyprenylated acylphloroglucinols with a major bicyclo[3.3.1]nonane-2,4,9-trione skeleton. Notably, compound 1 is a rare PPAP with a hydroperoxy group, and a plausible biosynthetic pathway for 1 was proposed. Compounds 4 and 6 exhibited significant neuroprotective effects under 10 µM against corticosterone (CORT)-injured SH-SY5Y cells. Furthermore, compound 4 demonstrated a noteworthy antidepressant effect at the dose of 5 mg/kg in the tail suspension test (TST) of mice, which was equivalent to 5 mg/kg of fluoxetine. And it potentially exerted an antidepressant effect through the hypothalamic-pituitary-adrenal (HPA) axis.

The NLRP3 inflammasome in depression: Potential mechanisms and therapies.

Increasing evidence suggests that the failure of clinical antidepressants may be related with neuroinflammation. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is an intracellular multiprotein complex, and has been considered as a key contributor to the development of neuroinflammation. Inhibition of NLRP3 inflammasome is an effective method for depression treatment. In this review, we summarized current researches highlighting the role of NLRP3 inflammasome in the pathology of depression. Firstly, we discussed NLRP3 inflammasome activation in patients with depression and animal models. Secondly, we outlined the possible mechanisms driving the activation of NLRP3 inflammasome. Thirdly, we discussed the pathogenetic role of NLRP3 inflammasome in depression. Finally, we overviewed the current and potential antidepressants targeting the NLRP3 inflammasome. Overall, the inhibition of NLRP3 inflammasome activation may be a potential therapeutic strategy for inflammation-related depression.

New Rosane Diterpenoids and Their Analogs from Euphorbia ebracteolata Hayata.

Phytochemical investigation of the roots of Euphorbia ebracteolata Hayata resulted in the isolation of three new rosane diterpenoids, euphebracteolatins C-E (1-3), along with fourteen known analogs (4-17). Their structures were determined on the basis of extensive spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR. Euphebracteolatin C (1) contains a C-1/C-10 double bond and a keto group at C-7, and euphebracteolatins D and E (2-3) possess an aromatic ring-A in their skeleton. The plausible biogenetic pathways of all the isolates were also proposed. Furthermore, compounds 1 and 9 showed selective cytotoxicity against HepG2 cells with IC50 values of 14.29 and 12.33 µM, respectively, and 2-3 displayed moderate cytotoxicity against three human cancer lines, with IC50 values ranging from 23.69 to 39.25 µM.

Phytochemistry, synthesis, analytical methods, pharmacological activity, and pharmacokinetics of loganin: A comprehensive review.

Iridoid glycosides (IGs) are found in many medicinal and edible plants, such as Gardenia jasminoides, Cistanche tubulosa, Eucommia ulmoides, Rehmanniae Radix, Lonicera japonica, and Cornus officinalis. Loganin, an IG, is one of the main active ingredient of Cornus officinalis Sieb. et Zucc., which approved as a medicinal and edible plant in China. Loganin has been widely concerned due to its extensive pharmacological effects, including anti-diabetic, antiinflammatory, neuroprotective, and anti-tumor activities, etc. Studies have shown that these underlying mechanisms include anti-oxidation, antiinflammation and anti-apoptosis by regulating a variety of signaling pathways, such as STAT3/NF-κB, JAK/STAT3, TLR4/NF-κB, PI3K/Akt, MCP-1/CCR2, and RAGE/Nox4/p65 NF-κB signaling pathways. In order to better understand the research status of loganin and promote its application in human health, this paper systematically summarized the phytochemistry, analysis methods, synthesis, pharmacological properties and related mechanisms, and pharmacokinetics based on the research in the past decades.

Jolkinolide B alleviates renal fibrosis via anti-inflammation and inhibition of epithelial-mesenchymal transition in unilateral ureteral obstruction mice.

Renal fibrosis is a critical pathological process lead to a progressive loss of renal function. Jolkinolide B (JB) is a natural compound with anti-inflammatory activity from Euphorbia fischeriana Steud. The study evaluated the effect of JB on renal fibrosis in mice with unilateral ureteral obstruction (UUO). The results showed that JB could decrease renal fibrotic area, reduce phosphorylation of NF-κB p65 and the release of TNF-α, IL-6 and IL-1ß, restore the expression of vementin, α-SMA and E-cadherin, as well as TGF-ß1 and p-smad2/3. In conclusion, JB might reduce renal fibrosis by inhibiting inflammation induced by NF-κB pathway and EMT mediated by TGF-ß1/Smad pathway.

Fischdiabietane A, an Antitumoral Diterpenoid Dimer Featuring an Unprecedented Carbon Skeleton from Euphorbia fischeriana.

Fischdiabietane A (1), a novel asymmetric diterpenoid dimer with a unique nonacyclic 6/6/6/5/7/6/6/6/6 ring system possessing unprecedented 2-oxaspiro[4.5]decane-1-one and 2-oxabicyclo[3.2.2]nonane frameworks in D/E/F rings, was isolated from the roots of Euphorbia fischeriana. Its structure was determined by spectroscopic techniques, electronic circular dichroism calculations, and X-ray diffraction experiments. Notably, 1 is the first abietane-type [4 + 2] Diels-Alder dimer identified from nature. The IC50 of 1 against T47D cells was about sixfold higher than that of cisplatin (the positive control). Furthermore, 1 induced apoptosis in T47D cells through the activation of caspase-3 and the degradation of poly(ADP-ribose) polymerase.

Secoiridoid dimers and their biogenetic precursors from the fruits of Cornus officinalis with potential therapeutic effects on type 2 diabetes.

Cornusdiridoid A-F (1-6), six unusual cornuside-morroniside secoiridoid dimers, and their possible new biogenetic precursor, 3″,5″-dehydroxycornuside (7), together with four known secoiridoids (8-11), were obtained from the fruits of Cornus officinalis. Their structures were elucidated on the basis of various spectroscopic and chemical methods. A plausible biosynthetic pathway of compounds 1-11 was proposed. The α-glucosidase inhibitory, antioxidant and anti-inflammatory activities of these isolates were evaluated. Some of them emerged out as potent antidiabetic, anti-inflammatory and free radical scavenging agents. Molecular docking was also carried out for antidiabetic target α-glucosidase to investigate the possible binding modes of the most potent α-glucosidase inhibitor, vincosamide (9). These results revealed that the secoiridoids from C. officinalis fruits may be served as new potential antidiabetic agents to prevent and treat type 2 diabetes.

Fischeriana A, a meroterpenoid with an unusual 6/6/5/5/5/6/6 heptacyclic carbon skeleton from the roots of Euphorbia fischeriana.

Fischeriana A (1), a new meroterpenoid with a rare carbon skeleton, along with one of its known biosynthesis-related compounds 2,4-dihydroxy-6-methoxyacetophenone (2) and two known ent-abietane-type diterpenoids (3-4), were isolated from the roots of Euphorbia fischeriana. Their structures, including the stereochemistry, were elucidated using comprehensive spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analysis. Compound 1 was found to be made up of an unusual heptacyclic ring system (6/6/5/5/5/6/6) featuring a modified ent-abietane diterpene with a phloroglucinol moiety. A possible biogenetic pathway for 1 was proposed. Compound 1 exhibited marked anti-tumor activities against the HepG2 cell line.

Unusual cadinane-type sesquiterpene glycosides with α-glucosidase inhibitory activities from the fruit of Cornus officinalis Sieb. et Zuuc.

Five novel and rare cadinane-type sesquiterpene glycosides, cornucadinoside A-E (1-5) were isolated from water extract of the fruit of Cornus officinalis Sieb. et Zuuc.. The new chemical structures, together with their absolute configurations, were elucidated on the basis of extensive spectroscopic analysis, including a comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. Their structures, which possess a naphthalene skeleton, are the first report on the occurrence of cadinane sesquiterpene glycosides in Cornus. Additionally, all the compounds exhibited marked α-glucosidase inhibitory activity except for 3in vitro.

Cornusglucosides A and B, Two New Iridoid Glucosides from the Fruit of Cornus officinalis.

Phytochemical study on the fruit of Cornus officinalis Sieb. et Zucc. yielded two new iridoid glucosides, named cornusglucoside A (1) and cornusglucoside B (2). The structures of 1 and 2 were elucidated via comprehensive NMR and HR-ESI-MS data analysis. Additionally, their inhibitory effects on IL-6-induced STAT3 activation were assessed.

Daturanolide A-C, Three New Withanolides from Datura metel L. and Their Cytotoxic Activities.

Three new withanolides (1-3), named as daturanolide A-C, along with six known withanolides (4-9) were isolated from the flowers of Datura metel L. Their structures with absolute configurations were elucidated by a series of spectroscopic methods, electronic circular dichroism (ECD) analyses, and X-ray crystallography. All the isolates were evaluated for cytotoxicity against five human cancer cell lines (HCT116, U87-MG, NCI-H460, BGC823, and HepG2), and 6 exhibited marked cytotoxicity.

[A new lignan from rhizome of Stellera chamaejasme].

To investigate the chemical compounds from the rhizome of Stellera chamaejasme, nine lignans, including stellerachamin A (1), 8-hydroxypluviatolide (2), wikstromol (3), pinoresinol (4), matairesinol (5), dextrobursehernin (6), hinokinin(7), (-)-glaberide I (8) and （-） medioresinol (9) were isolated by various chromatographic methods. Their structures were extensively determined on basis of MS and NMR spectroscopic data analysis. Among them, compound 1 was a new lignan, and compounds 2 and 7 were isolated from Thymelaeaceae for the first time.

[A new phenylpropanoid glycoside from fruit of Cornus officinalis].

To investigate the chemical compounds from the ripe fruit of Cornus officinalis, a new phenylpropanoid glycoside 1-O-(6'-O-p-hydroxybenzoyl-ß-D-glucopyranosyl)-p-phenylpropanol, named cornuphenylpropanoid A (1), were separated and purified by D101 macroporous resin, silica gel and ODS column chromatography. Its structure was extensively determined on basis of ¹H-NMR, ¹³C-NMR, DEPT, HSQC, HMBC and HR-ESI-MS spectroscopic data.

Cornusides A-O, Bioactive Iridoid Glucoside Dimers from the Fruit of Cornus officinalis.

Fifteen new and rare iridoid glucoside dimers, cornusides A-O (1-15), and 10 known iridoid glucosides (16-25) were isolated from the fruit of Cornus officinalis. These new chemical structures were established through spectroscopic analysis (UV, IR, HRESIMS, 1D and 2D NMR). Compounds 1-25 were tested for their inhibitory activities by measuring IL-6-induced STAT3 promoter activity in HepG2 cells, and 3, 12, 17, 22, and 23 showed inhibitory effects, with IC50 values of 11.9, 12.2, 14.0, 7.0, and 6.9 µM, respectively.

[Preparation and identification of Jujuboside A artificial antigen].

Immunogenic antigen (jujuboside A-BSA) and coating antigen (jujuboside A-OVA) of jujuboside A were synthesized by sodium periodate oxidation method for the first time. Jujuboside A artificial antigen was confirmed by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF-MS). The titer and specificity of the antibody in serum of immunized mice were detected by enzyme-linked immunosorbent assay (ELISA). The corrected relation curve of inhibition rate showed that the antibody against Jujuboside A obtained from immunized mice could bind to jujuboside A and the titer was up to 1∶4 000. The jujuboside A artificial antigen was synthesized, which can be used further to preparation of monoclonal antibody and the pharmacokinetics study of jujuboside A in laboratory animals.

[Chemical constituents from ripe fruit of Cornus officinalis].

To investigate the chemical compounds from the fruit of Cornus officinalis, six compounds were isolated and determined by extensive spectroscopic analysis as 6'-O-acetyl-7α-O-ethyl morroniside (1), (-)-isolariciresinol 3α-O-ß-D-glucopyranoside(2), apigenin (3), cirsiumaldehyde(4), p-coumaric acid (5), caffeic acid (6). Compound 1 was a new iridoid glucoside,and compounds 2-4 were obtained from the Cornus genus for the first time. Compounds 2-6 were evaluated for the viability of PC12 cells when exposed in conditions of oxygen and glucose deprivation. The MTT results showed that compound 4 increased cell viability moderately in OGD/R treated PC12 cells at the concentration of 1.0 µmol•L⁻¹.

Renoprotective effect of berberine on type 2 diabetic nephropathy in rats.

Inflammation, fibrosis, and lipid disorder are essential promoters in the pathogenesis of diabetic kidney injury in diabetes mellitus type 2. Berberine (BBR) has been reported to have beneficial effects on diabetic nephropathy, but its action mechanism is still unclear. The present study was designed to elucidate the therapeutic mechanism of BBR in a type 2 diabetic nephropathy rat model induced by a high-fat diet and low-dose streptozotocin injection. The diabetic rats were treated with or without BBR by gavage for 20 weeks and examined by serology, 24-h albuminuria, histology, immunohistochemistry, and molecular analyses. Results showed that treatment with BBR significantly reduced serum levels of blood glucose and lipids, inhibited urinary excretion of albumin, and attenuated renal histological injuries in diabetic rats. Berberine treatment also inhibited renal inflammation, which was associated with inactivation of nuclear factor kappa-light-chain-enhancer of activated B-cell signalling. As a result, the upregulation of pro-inflammatory cytokines (interleukin-1ß, tumour necrosis factor-α) and chemokine (monocyte chemotactic protein-1) was blocked. In addition, BBR treatment also inactivated transforming growth factor-ß/Smad3 signalling and suppressed renal fibrosis, including expression of fibronectin, collagen I, and collagen IV. The present study reveals that BBR is a therapeutic agent for attenuating type 2 diabetic nephropathy by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cell-driven renal inflammation and transforming growth factor-ß/Smad3 signalling pathway.

Three new cyathane diterpenoids from the medicinal fungus Cyathus africanus.

Three new cyathane diterpenoids, cyathin W (1), cyathin V (2), and cyathin T (3), were isolated from the solid culture of Cyathus africanus. The structures and configurations of these new compounds were elucidated on the basis of comprehensive spectroscopic analysis including 1D NMR, 2D NMR (HSQC, HMBC, NOESY), and HR-ESI-MS experiments. Compounds 1 and 3 showed moderate inhibition against nitric oxide production in lipopolysaccaride-activated macrophages with IC50 value of 80.07 and 88.87 µM, respectively. In cytotoxicity assay, compound 1 showed weak cytotoxicity against K562 cell line with IC50 value of 12.1 µM.

[Pharmacokinetics of salvianolic acid A after single intravenous administration in Rhesus monkey].

Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) µg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.

[Chemical constituents from aerial part of Rehmannia glutinosa].

To investigate the chemical compounds from aerial part of Rehmannia glutinosa, six compounds were isolated and deter- mined by extensive spectroscopic analysis as(+)-(7S, 8S, 8'S)-9-O-[ß-D-glucopyranoyl] asarininone(1), 2α,3ß,19α,23-tetrahydroxy-olean-12-en-28-oic acid(2),7,3'-dihydroxyl-5'-methoxyisoflavone (3), aeginetic acid (4), corchorifattty acid B (5), pinellic acid (6). Among them, compound 1 was a new natural product. Compounds 2, 3 and 5 were obtained from the Rehmannia genus for the first time. In vitro study showed that none of the six compounds exhibited obvious activities to BEL-7402 and HCT-8 at the concentration of 10 mg x L(-1).