Hedscandines A-C, three undescribed indole alkaloids from Hedyotis scandens with their anti-MRSA activity.

Hedscandines A-C (1-3), three undescribed indole alkaloids were isolated from Hedyotis scandens Roxb, a traditional Chinese medicine widely used in the treatment of respiratory ailments. Their structures were elucidated by extensive spectroscopic data and electronic circular dichroism calculation. Hedscandine A (1), possessed a unique carbon skeleton with a 1,4-oxazonin-2(3H)-one core system and displayed a rapid bactericidal activity against MRSA with a MIC value of 16 µg/mL. Mechanistic studies showed that compound 1 could disrupt the integrity of bacterial cell membranes and thus lead to bacterial death.

[Chemical constituents from whole herb of Hedyotis scandens].

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 µg·mL~(-1), respectively.

Inhibition of SND1 overcomes chemoresistance in bladder cancer cells by promoting ferroptosis.

Chemotherapy remains one of the most important adjuvant treatments for bladder cancer (BC). However, similar to other malignancies, BC is prone to chemotherapy resistance and only approximately half of muscle­invasive patients with BC respond to chemotherapy. The present study aimed to reveal the mechanisms underlying chemoresistance in BC cells. Cell viabilities were assessed by CCK­8 assay. The differentiated expression of genes in chemoresistant and their parental BC cells were examined by RNA sequencing. Cell death was determined by flow cytometry. Different cell death inhibitors were used to determine the types of cell death. Levels of reactive oxygen species, iron, glutathione and malondialdehyde were assessed using the corresponding commercial kits. ChIP and dual luciferase activity assays were performed to investigate the interaction between staphylococcal nuclease and tumour domain containing 1 (SND1) and glutathione peroxidase 4 (GPX4) mRNA. RNAi was used to knockdown SND1 or GPX4. The results revealed that SND1 in BC cells were insensitive to cisplatin, and inhibition of SND1 overcame this resistance. Silencing of SND1 enhanced cell death induced by cisplatin by promoting ferroptosis in BC cells. Mechanistically, SND1 was revealed to bind to the 3'UTR region of GPX4 mRNA and stabilise it. Knockdown of GPX4 could also overcome chemoresistance, and overexpressing GPX4 reversed the effects of silencing of GPX4 on the chemosensitivity of BC cells. Thus, targeting the SND1­GPX4 axis may be a potential strategy to overcome chemoresistance in BC cells.

Pu-erh tea increases the metabolite Cinnabarinic acid to improve circadian rhythm disorder-induced obesity.

Obesity is one of the circadian rhythm disorders (CRD)-mediated metabolic disorder syndromes. Pu-erh tea is a viable dietary intervention for CRD, however its effect on CRD-induced obesity is unclear. Here, we found that Pu-erh tea improved obesity in CRD-induced mice, which stemmed from the production of Cinnabarinic acid (CA). CA promoted adipose tissue lipolysis and thermogenic response (HSL, ATGL, Pparα, CKB, UCP1) and increased adipocyte sensitivity to hormones and neurotransmitters by targeting the expression of adipose tissue receptor proteins (Q6KAT8, P51655, A2AKQ0, M0QWX7, Q6ZQ33, and mGluR4). This improved mitochondrial activity and facilitated adipose tissue metabolic processes, thereby accelerating glucolipid metabolism. Also, CA-induced alterations in gut microbes and short-chain fatty acids further improved CRD-mediated lipid accumulation. These results suggest that the increase of CA caused by Pu-erh tea, targeted to adipose tissue via the metabolite-blood circulation-adipose tissue axis, maybe a key mechanism for reducing the development of CRD-induced obesity.

[Secondary metabolites of endophyte fungi Xylaria sp. from Coptis chinensis].

Two new polyketides, lasobutone A(1) and lasobutone B(2), along with three known compounds, guignardianone C(3), guignardic acid(4), and 4-hydroxy-17R-methylincisterol(5), were isolated from the endophytic fungi Xylaria sp. by silica gel, MCI, and preparative HPLC, which was separated from the Chinese medicinal material Coptis chinensis and cultivated through solid fermentation with rice. Their structures were elucidated on the basis of spectroscopic methods, such as MS, NMR, IR, UV, and ECD. Compounds 2 and 4 showed inhibitory activities against the nitric oxide(NO) production in the LPS-induced macrophage RAW264.7 with IC_(50) values of 58.7 and 42.5 µmol·L~(-1) respectively, while compound 5 exhibited cytotoxic activities against HT-29 with IC_(50) value of 14.3 µmol·L~(-1).

[A new polyketide of endophytic fungi Aspergillus sp. ZJ-58 from Coptis chinensis].

A new polyketide, coptaspin A(1), along with two known compounds 4-acetyl-3,4-dihydro-6,8-dihydroxy-3-methoxy-5-methylisocoumarin(2), and cytochalasin Z_(12)(3), was isolated from the endophytic fungi Aspergillus sp. ZJ-58, which was isolated from the genuine medicinal plant Coptis chinensis in Chongqing after solid-state fermentation on rice and silica gel, MCI, and HPLC-based separation. Their structures were elucidated by MS, NMR, IR, UV, and ECD. The newly isolated compound 1 showed moderate inhibitory activities against LPS-induced NO production in RAW264.7 macrophages with the IC_(50) value of 58.7 µmol·L~(-1), suggesting its potential anti-inflammatory activity.

14-Membered resorcylic acid lactone derivatives with their anti-inflammatory from the fungus Aspergillus sp. ZJ-65.

Two new 14-membered resorcylic acid lactone derivatives, ascarpins A (1) and B (2), together with three related known compounds (3-5) were isolated from the fungus Aspergillus sp. ZJ-65, obtaining from the intestine of grass carp. These structures were elucidated on the basis of extensive spectroscopic methods, chemical conversion, and comparison with literature. All isolates were tested for their inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages. Among them, compounds 1-4 exhibited potential anti-inflammatory activity with IC50 values ranging from 7.6 to 48.3 µM.

[Biotransformation and enzymatic mechanism of protoberberine alkaloids].

Protoberberine alkaloids belong to the quaternary ammonium isoquinoline alkaloids, and are the main active ingredients in traditional Chinese herbal medicines, like Coptis chinensis. They have been widely used to treat such diseases as gastroenteritis, intestinal infections, and conjunctivitis. Studies have shown that structural modification of the protoberberine alkaloids could produce derivative compounds with new pharmacological effects and biological activities, but the transformation mechanism is not clear yet. This article mainly summarizes the researches on the biotransformation and structure modification of protoberberine alkaloids mainly based on berberine, so as to provide background basis and new ideas for studies relating to the mechanism of protoberberine alkaloids and the pharmacological activity and application of new compounds.

[Effects of the Radix Ranuncoli Ternati extracts on Mycobacterium tuberculosis proteome profiling revealed by 2D electrophoresis].

Radix Ranuncoli Ternati is clinically effective traditional Chinese medicine for multidrug resistant tuberculosis. Its active components and mechanism of action remain unsolved. Two dimensional gel electrophoresis (2-DE) was employed to address this problem. Globlal proteome of Mycobacterium tuberculosis untreated and treated with Radix Ranuncoli Ternati were compared, and 22 protein spots were found to be expressed differentially. 3 protein spots which remarkably decreased in Mycobacterium tuberculosis treated with Radix Ranuncoli Ternati were subjected to matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) analysis. The data obtained from peptide mass finger printing were used for database search. The 3 protein spots in gel were identified as cysA2 (thiosulfate sulfurtransferase), tsf (elongation factor EF-Ts) and hspX (heat shock protein X). These data provide insights into the changed global protein patterns of Mycobacterium tuberculosis treated with Radix Ranuncoli Ternati and may prove useful for further study in the mechanism in how Radix Ranuncoli Ternati influence the life of Mycobacterium tuberculosis. The differentially expressed proteins may be potential novel antituberculosis drug targets.