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.

Biologically active secoiridoids: A comprehensive update.

Secoiridoids are natural products of cyclopentane monoterpene derivatives that are formed by splitting the rings of cyclomethene oxime compounds at C-7 and C-8, and only account for a small part of cyclic ether terpenoids. Because of the chemically active hemiacetal structure in their common basic skeleton, secoiridoids have a wide range of biological activities, such as neuroprotective, anti-inflammatory, antidiabetic, hepatoprotective, and antinociceptive activities. Phenolic secoiridoids can also act against multiple molecular targets involved in human tumorigenesis, making them potentially valuable precursors for antitumor drug development. This review provides a detailed update, covering relevant discoveries from January 2011 to December 2020, about the occurrence, structural diversity, bioactivities, and synthesis of naturally occurring secoiridoids. We aimed to resolve the lack of extensive, specific, and thorough review of secoiridoids, as well as open new areas for pharmacological investigation and better drugs based on these compounds.

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.

Cornuside, by regulating the AGEs-RAGE-IκBα-ERK1/2 signaling pathway, ameliorates cognitive impairment associated with brain aging.

Anti-Alzheimer's disease (AD) drugs can only change the symptoms of cognitive impairment in a short time but cannot prevent or completely cure AD. Thus, a more effective drug is urgently needed. Cornuside is extracted from Corni Fructus, a traditional Chinese medicine that plays an important role in treating dementia and other age-related diseases. Thus, the study aimed to explore the effects and mechanisms of Cornuside on the D-galactose (D-Gal) induced aging mice accompanied by cognitive decline. Initially, we found that Cornuside improved the learning and memory abilities of D-Gal-treated mice in behavioral experiments. Pharmacological experiments indicated that Cornuside acted on anti-oxidant and anti-inflammatory effects. Cornuside also reversed acetylcholin esterase (AChE) activity. Meanwhile, pathology tests showed that Cornuside had a protective effect on neuron damage. Cornuside increased the expression of brain-derived neurotrophic factor (BDNF), and down-regulated the expression of receptor for advanced glycosylation end products (RAGE), ionized calcium binding adapter molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP) respectively. Further studies claimed that Cornuside had important effects on the expression of IκBα and extracellular signal-regulated kinases 1/2 (ERK1/2). These effects might be achieved through regulating the AGEs-RAGE-IκBα-ERK1/2 signaling pathway, among which, ERK1/2 might be the key protein. The study provides direct preclinical evidence for the research of Cornuside, which may become an excellent candidate drug for the treatment of aging-related AD.

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.

Hyperammonemia in a septic patient with Ureaplasma parvum arthritis: a case report.

BACKGROUND: Septic arthritis requires prompt diagnosis and treatments. Rare pathogens should be considered when patients respond poorly to the initial antibiotic treatments. Ureaplasma parvum is an opportunistic pathogen that commonly resides in the human urogenital tract. Its infection commonly causes hyperammonemia. Hyperammonemia from Ureaplasma parvum septic arthritis has never been reported previously. CASE PRESENTATION: A 65-year-old male presented with fever and left lower leg pain and swelling for more than ten days. Septic arthritis and sepsis were considered after laboratory tests and arthrocentesis. However, he responded poorly to the antibiotic treatments, including cefoperazone-sulbactam, imipenem-cilastatin, and linezolid. His mental status deteriorated rapidly with elevated blood ammonia levels with unremarkable liver function test and sonogram examination results. Despite the treatments with lactulose, L-ornithine L-aspartate, mannitol, and hemodialysis therapy to lower his ammonia level, his blood ammonia level remained persistently high. Finally, metagenomic sequencing of the left knee synovial fluid reported Ureaplasma parvum, which was considered to contribute to his hyperammonemia. CONCLUSION: Ureaplasma parvum could cause septic arthritis with hyperammonemia. Genetic tests, such as polymerase chain reaction and next-generation sequencing techniques, could provide a sensitive and fast diagnosis of Ureaplasma parvum.

Concurrent severe pulmonary tuberculosis with Evans syndrome: a case report with literature review.

BACKGROUND: Tuberculosis is a bacterial infection involving multiple organs and systems. Its hematological presentation mainly includes anemia and leukocytosis. Evans syndrome is a rare autoimmune disease characterized by autoimmune hemolytic anemia, immune thrombocytopenia, and neutropenia, with positive results for the direct Coombs test and platelet antibodies. The cooccurrence of tuberculosis and Evans syndrome is rarely reported. CASE PRESENTATION: A 69-year-old female presented with a fever and shortness of breath. Her chest computerized tomography scan showed extensive miliary nodules in the bilateral lung fields. She rapidly developed respiratory failure that required endotracheal intubation and mechanical ventilation. The acid-fast bacilli sputum smear results indicated a grade of 3+. Later on, blood testing revealed hemolytic anemia, a positive direct Coombs test result, and the presence of the platelet antibody IgG. This patient was diagnosed as having disseminated pulmonary tuberculosis and Evans syndrome. She successfully recovered after treatment with antituberculosis drugs and glucocorticoids. CONCLUSIONS: Tuberculosis can occur together with Evans syndrome. Affected patients should receive both antituberculosis and immunosuppressive drugs.

The Correlation between 25-Hydroxyvitamin D3 and the Severity and Short-Term Prognosis of Pulmonary Tuberculosis.

BACKGROUND: Pulmonary tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis in the lungs. The present study aims to investigate the correlation between serum 25-hydroxyvitamin D3 (25-VD3) and the severity and short-term prognosis of tuberculosis. METHODS: The clinical data of 261 pulmonary tuberculosis patients, who were admitted to the Tuberculosis Diagnosis and Treatment Center of our hospital from January 1, 2017 to December 31, 2020, was retrospectively collected. Taking the median of 25-VD3 at admission (11.40 ng/mL) as the cutoff value, these patients were divided into two groups: high 25-VD3 group (> 11.40 ng/mL, n = 131) and low 25-VD3 group (≤ 11.40 ng/mL, n = 130). Then, Pearson's correlation analysis was performed using SPSS to determine the correlation between the 25-VD3 level and the length of hospitalization and Acute Physiology and Chronic Health Evaluation II (APACHE II) score of pulmonary tuberculosis patients. According to the clinical outcome after 28 days of treatment, these patients were divided again into two groups: improvement group (n = 170) and death group (n = 91). Then, Pearson's correlation analysis through SPSS was performed to determine the relationship between the 25-VD3 level and short-term prognosis of pulmonary tuberculosis patients. RESULTS: Compared to the low 25-VD3 group, pulmonary tuberculosis patients in the high 25-VD3 group were younger, had a higher percentage of improvement after 28 days of treatment, and had a lower APACHE II score (p < 0.05). However, the 25-VD3 level was not significantly correlated to the length of hospital stay of pulmonary tuberculosis patients (correlation coefficient r = 0.020, p = 0.746) and was significantly negatively correlated to the APACHE II score (correlation coefficient r = -0.211, p = 0.001). In addition, the age and APACHE II score of patients were lower in the improvement group, when compared to the death group, while the 25-VD3 level was higher and the length of hospital stay was longer, when compared to the death group (p < 0.01). The logistic regression analysis revealed that the length of hospital stay, APACHE II score, and 25-VD3 level are independent risk factors that affect the prognosis of pulmonary tuberculosis patients (p < 0.05). CONCLUSIONS: In summary, 25-VD3 is closely correlated to the severity of tuberculosis, and this can be used to evaluate and predict the prognosis of patients.

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.

Misdiagnosed tuberculosis being corrected as Nocardia farcinica infection by metagenomic sequencing: a case report.

BACKGROUND: Disseminated nocardiosis is liable to be misdiagnosed owing to the non-specific clinical manifestations and laboratory/imaging findings. Metagenomic next-generation sequencing (mNGS) is a culture-independent and rapid method for direct identification of all microorganisms in clinical specimens. CASE PRESENTATION: A 72-year-old man was admitted to our hospital on February 20, 2019 with a history of recurrent cough, expectoration, fever, and diarrhea since 1 month, and unconsciousness since 1 week. Contrast-enhanced magnetic resonance imaging of head showed multiple lesions in the bilateral cerebral hemispheres, brainstem, and cerebellar hemispheres. The presumptive diagnosis was disseminated tuberculosis, although all tests for mycobacterium were negative. However, the patient did not benefit from antituberculosis treatment. Repeat MRI showed multiple abnormal signals in the brain and progression of meningeal thickening. Cerebrospinal fluid and bronchoalveolar lavage fluid specimens were subsequently sent for PMSeq metagenomics sequencing; the results indicated Nocardia. farcinica as the predominant pathogen. The anti-TB treatment was stopped and the patient was prescribed sulphamethoxazole in combination with linezolid and meropenem for nocardiosis. He showed gradual neurological improvement and was transferred to Huashan Hospital. He was discharged from the hospital on April 19, 2019, but died of persistent diarrhea on May 26, 2019. CONCLUSIONS: Patients with suspected nocardiosis do not always respond to conventional treatment; therefore, mNGS can facilitate diagnosis and timely treatment decision-making.

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.

APACHE-II score for anti-tuberculosis tolerance in critically ill patients: a retrospective study.

BACKGROUND: To investigate the status of anti-tuberculosis treatment in critically ill patients, and to explore the value of APACHE-II score in guiding anti-tuberculosis treatment. METHODS: This analysis included critically ill patients with tuberculosis. The utility of APACHE-II score for predicting drug withdrawal was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Among 320 patients enrolled (58 ± 22 years; 256 males), 147 (45.9%) had drugs withdrawn. The drug withdrawal group had higher APACHE-II score (median [interquartile range]: 21 [3-52] vs. 17 [4-42] points), higher CD4%, lower hemoglobin level, higher rates of chronic obstructive pulmonary disease (COPD) and chronic renal failure, and lower rate of extrapulmonary tuberculosis (P < 0.05). Logistic regression identified APACHE-II score > 18 (odds ratio [95% confidence interval]: 2.099 [1.321-3.334], P < 0.01), COPD (1.913 [1.028-3.561], P < 0.05) and hemoglobin level (0.987 [0.977-0.997], P < 0.05) as independent factors associated with drug withdrawal. At an optimal cutoff of 18.5, the sensitivity, specificity, positive predictive value and negative predictive value of APACHE-II score for predicting drug withdrawal was 59.2, 61.8, 56.9 and 64.1%, respectively. CONCLUSIONS: APACHE-II score > 18 points might predict patient tolerance of anti-tuberculosis treatment.

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 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.

[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.