Old fusidane-type antibiotics for new challenges: Chemistry and biology / 中国天然药物

The spread of antibiotic-resistant bacteria and exhausted drug leads render some infections untreatable now and in the future. To deal with these "new challenges", scientists tend to re-pick up "old antibiotics". Fusidane-type antibiotics have been known for nearly 80 years as potent antibacterial agents against gram-positive bacteria, especially Staphylococci, and represent the only triterpene-derived antibiotic class in clinical setting. These attractive characteristics have drawn renewed attention on fusidane-type antibiotics in recent decades. Isolation, characterization, biological evaluation, as well as chemical modifications of fusidane-type antibiotics are increasingly being reported. Combinatorial biosynthesis of this type of antibiotics has been successfully utilized not only for elucidating the biosynthetic pathways, but also for expanding their structural diversity. Some isolated and synthetic compounds exhibit comparable or even more potent biological activity than fusidic acid. This review provides an overview of progress on the studies of structure and biology of fusidane-type antibiotics from 1943 to April 2021. The informative structure-activity relationship is also highlighted.

Two natural molecules preferentially inhibit azole-resistant Candida albicans with MDR1 hyperactivation / 中国天然药物

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.

Secondary metabolites from Colletotrichum fioriniae F18, an endophytic fungus isolated from the medicinal plant Mahonia fortunei / 药学学报

Chemical investigation on the rice culture of an endophytic fungus Colletotrichum fioriniae F18, inhabiting in the stems of the medicinal plant Mahonia fortunei, led to the isolation of nine compounds. They included a new indole alkaloid, makomotindoline B (1), and two known indole derivatives, 3-indoleacetic acid methyl ester (2) and N-acetyltryptamine (3), together with six known aromatic compounds, 2-(4-hydroxyphenyl) acetic acid (4), 4-(2-hydroxyethyl)phenol (5), 2-(4-methoxyphenyl)acetic acid (6), 4-hydroxyphenethyl 2-(4-hydroxyphenyl)acetate (7), regiolone (8) and N-phenethylacetamide (9). The structures of these compounds were elucidated based on the analysis of spectroscopic data including MS and NMR. The absolute configuretion of compound 1 was determined by electronic circular dichroism (ECD) calculation. Antibacterial activity assay indicated that compounds 1-9 had no antibacterial activities against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, as well as no quorum sensing inhibitory (QSI) activity for Chromobacterium violaceum.

Pre-treatment with puerarin affects pharmacokinetics of warfarin, but not clopidogrel, in experimental rats / 中国天然药物

The present study was designed to determine the effects of puerarin pre-treatment on the pharmacokinetics of the oral anticoagulant agent warfarin and the antiplatelet agent clopidogrel in rats. In the treatment group, rats was gavaged with warfarin or clopidogrel after repeated treatment with puerarin at intraperitoneal doses of 20, 60, or 200 mg·kg(-1) for 7 days, while rats in the control group were administrated only with the same dose warfarin or clopidogrel. Plasma samples were obtained at the prescribed times and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The results showed that rats treated with puerarin at all the test doses of 20, 60 and 200 mg·kg(-1) were found to affect the pharmacokinetics of warfarin, but not clopidogrel, suggesting a potential herb-drug interaction between puerarin and warfarin.

Scapaundulin C, a novel labdane diterpenoid isolated from Chinese liverwort Scapania undulate, inhibits acetylcholinesterase activity / 中国天然药物

In the present study, scapaundulin C (1), a new labdane diterpenoid, and four related known compounds scapaundulin A (2), 5α, 8α, 9α-trihydroxy-13E-labden-12-one (3), 5α, 8α-dihydroxy-13E-labden-12-one (4), and (13S)-15-hydroxylabd-8 (17)-en-19-oic acid (5), were isolated from the Chinese liverwort Scapania undulate (L.) Dum., using column chromatography. The structures of these compounds were determined on the basis of 1D- and 2D-NMR analyses. The acetylcholinesterase (AchE) inhibitory activity was evaluated using a bioautographic TLC assay and the cytotoxic activity was evaluated by the MTT method. All the compounds were reported for the first time to exhibit moderate AchE inhibitory activity with minimal inhibitory quantities ranging from 250 to 500 ng. All the compounds were tested for their cytotoxicity against five human tumor cell lines, A549, K562, A2780, Hela, and HT29, and compounds 3 and 4 exhibited moderate inhibitory effects on the growth of A2780 cells.

LC-MS/MS method for the determination of a new puerarin derivative and its application in pharmacokinetic studies in rats / 中国天然药物

AIM@#To establish a sensitive and rapid liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of dehydrated puerarin in rat plasma, and its application for pharmacokinetic studies.@*METHODS@#A plasma sample was pretreated by one-step protein precipitation by the addition of five volumes of methanol. The chromatographic separation was achieved on a Zorbax SB-C18 column (4.6 mm × 150 mm I.D. 5.0 μm, Agilent, USA) at 40 °C at a flow rate of 0.6 mL·min(-1) by an isocratic elution consisting of 10 mmol·L(-1) ammonium acetate in methanol and water containing 0.1% formic acid in a ratio of 20 : 80 (V/V). Detection was performed on a triple quadrupole mass spectrometer in multiple-reaction monitoring (MRM) mode. An atmospheric pressure chemical ionization (APCI) interface in positive ionization mode was used by monitoring the transitions from m/z 399.1→281.0 (dehydrated puerarin) and m/z 271.0→215.0 (internal standard, IS).@*RESULTS@#Calibration curves were linear in the concentration range from 1.50 to 5400 ng·mL(-1), and the lower limit of quantification (LLOQ) was 1.50 ng·mL(-1) in rat plasma. The accuracy and precision values, which were calculated from three different sets of quality control samples analyzed in sextuplicate on three different days, ranged from 95.73% to 103.18%, and from 4.33% to 7.86%, respectively.@*CONCLUSION@#The method was successfully applied to assess the pharmacokinetics of dehydrated puerarin after oral administration in rats.

Induction of actin disruption and downregulation of P-glycoprotein expression by solamargine in multidrug-resistant K562/A02 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Solamargine (SM), a steroidal glycoalkaloid isolated from the Chinese herb Solanum incanum, has been shown to inhibit the growth of some cancer cell lines and induce significant apoptosis. However, the effects of SM on multidrug-resistant (MDR) cells and the molecular mechanisms involved are poorly understood. The purpose of this study was to evaluate the anti-MDR effects of SM and the associated mechanisms in MDR K562/A02 cells.</p><p><b>METHODS</b>The cytotoxicity of SM was measured by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. The 14',6-diamidino-2-phenylindole (DAPI) nuclear staining and flow cytometry were used to detect SM-induced apoptosis. The mRNA expression of P-glycoprotein (P-gp) was investigated by real-time PCR (RT-PCR). Western blotting was used to determine the expression of Bcl-2, Bax, and actin. The changes in the morphology of actin were examined with immunofluorescence staining.</p><p><b>RESULTS</b>MTT results showed that SM effectively killed the MDR sublines K562/A02, KB/VCR, and H460/paclitaxel (Taxol), and their parental cell lines K562, KB, and H460 to an equivalent or more sensitive degree. Based on the results by flow cytometry and immunostaining, the pro-apoptotic effects of SM were observed in MDR K562/A02 cells. Furthermore, the RT-PCR results showed that SM induced the downregulation of MDR1 mRNA. In addition, the expression of P-gp and actin was decreased in the SM-treated cells, as measured by western blotting and immunostaining.</p><p><b>CONCLUSIONS</b>These results demonstrate that SM effectively triggers apoptosis in MDR tumor cells, which is associated with actin disruption and downregulation of MDR1 expression. This compound may merit further investigation as a potential therapeutic agent that bypasses the MDR mechanism for the treatment of MDR tumors.</p>

An investigation on formation mechanisms and preparation of curcumin phospholipid complex / 中国中药杂志

The purpose of this study was to investigate the preparation and characteristics of curcumin phospholipid complex, including the effects of reaction time, reaction solvent, reaction concentration and reaction temperature. Preparation technology resulted in that 0.5 g curcumin and 10 g soy phospholipid dissolved in 100 mL anhydrous alcohol, were stirred 1 h in 50 degrees C waterbath, then steamed alcohol in decompression, collected solid residue and vacuum dried for 12 h. The physicochemical properties for the new complex including IR spectrometer, mass spectrograph and HNMR equipment were detected. As a result, the formation of the complex is based on the reaction between phospholipid polar group rounding phosphorus atom and curcumin. This result gave the evidence for the formation mechanism of phospholipid complex.

The tissue distribution in mice and pharmacokinetics in rabbits of oridonin-solid lipid nanoparticles / 药学学报

<p><b>AIM</b>To investigate the tissue distribution and pharmacokinetics of oridonin-solid lipid nanoparticles in animals.</p><p><b>METHODS</b>HPLC method was established to determine the concentration of oridonin in serum of rabbits and in different tissues of mice. The results after tail iv administration of oridonin and oridonin solid lipid nanoparticles were compared.</p><p><b>RESULTS</b>The relative tissue content of oridonin of solid lipid nanoparticles in the liver, spleen, lung, heart and kidney were 4.25%, 3.44%, 1.19%, 0.52% and 0.60%, respectively. The concentration-time curves of oridonin and oridonin solid lipid nanoparticles were both fitted to the three-compartment model. T(1/2)pi = 0.087 h, T(1/2)alpha = 1.65 h, T(1/2)beta = 32.36 h, V(C) = 0.66 mL.kg(-1).</p><p><b>CONCLUSION</b>Solid lipid nanoparticles could increase the hepatic and lienic targeting efficiency of oridonin in mice and improve its bioavailability. Solid lipid nanoparticles were helpful for oridonin to reach a long circulation time and were hopeful to be its novel drug carrier.</p>

Isolation and structure identification of grape seed polyphenols and its effects on oxidative damage to cellular DNA / 药学学报

<p><b>AIM</b>To isolate polyphenols from grape seeds and to evaluate their antioxidant effects.</p><p><b>METHODS</b>Pure compounds were isolated by using Diaion HP20, Toyopearl HW40 chromatography repeatedly, as well as semi-preparative RP-HPLC, from ethyl acetate extract of grape seeds. IR, MS, NMR, CD, X-Ray crystal diffraction spectral analysis were used to identify the structures. The antioxidant effects of different type of structures were screened by reducing power and DPPH (alpha,alpha-diphenyl-beta-picrylhydrazyl) free radical scavenging tests. Then, SCGE (single cell gel-electrophoresis) technique was used to investigate the effects of these potent antioxidant phytochemicals on cellular DNA oxidative damage with mice spleen cells, damage was induced by H2O2.</p><p><b>RESULTS</b>Eleven compounds were obtained including 3 novel structures, viniferones A, B and C. Proanthocyanidin B4, catecin, epicatechin and gallic acid showed strong antioxidant power, and at lower concentration (10 micromol x L(-1), 25 micromol x L(-1)), they can prevent cellular DNA damage, while 150 micromol x L(-1) catechin induced damage by itself.</p><p><b>CONCLUSION</b>Viniferones A, B and C were reported for the first time. That polyphenols investigated were shown to be good cellular DNA oxidative damage-preventing phytochemicals at lower concentration, could be used to explain the nutrient effect of grape seed polyphenols at certain degree. At the same time, higher concentration of polyphenols can induce oxidative damage, suggesting that dose is one factor to determine the nutrient effects.</p>

Determination of luteolin-7-O-glycoside in the herb of Dracocephalum rupestra by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a method for determination of luteolin-7-O-glycoside in the roots, stems, leafs, flowers and aerial parts of Dracocephalum rupestra sampled in different seasons.</p><p><b>METHOD</b>The samples were analyzed on an phenomenex C18 column, with mobile phase of methanol-acetonitrile-0.4% phosphoric acid (30:8:62) at flow rate 1.0 mL x min(-1) and detection at wavelength of 350 nm.</p><p><b>RESULT</b>The content of luteolin-7-O-glycoside in different parts of D. rupestra was different maximum in leaves, while minimum in stems. Luteolin-7-O-glycoside in D. rupestra sampled before blossoming was the highest.</p><p><b>CONCLUSION</b>The method simple, accurate and suitable for the quality evaluation of this plant medicine.</p>

Studies on IR fingerprint of tongren dahuoluo pills and tongren niuhuangqingxin pills / 中国中药杂志

<p><b>OBJECTIVE</b>To identify Tongren Dahuoluo pills and Tongren Niuhuangqingxin pills respectively by analysis of IR fingerprint.</p><p><b>METHOD</b>Both drugs were extracted with hexane, ethylether and butanone respectively and then the obtained extracts were measured with the ET-IR spectrometer.</p><p><b>RESULT</b>By analyzing IR fingerprint of 25 batches of Tongren Dahuoluo pills and 27 batches of Tongren Niuhuangqingxin pills, we found that different batches of the same drug hadstabile and repeatable fingerprint.</p><p><b>CONCLUSION</b>By using IR fingerprint, either Tongren Dahuoluo pills or Tongren Niuhuangqingxin pills can be exactly identified. It provides a rapid method for drug identification and quality control.</p>

Photosynthetic pigment contents of different germplasm of Rehmannia glutinosa and the relationship between pigments and leaf color / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the germplasm of Rehmannia glutinosa on the basis of photosynthetic pigment contents (PPC).</p><p><b>METHOD</b>20 cultivars were planted on the same condition. On Oct. 23 and Sept. 25, 3 leaves per cultivar were collected on different plants, and 80 mg mesophyll was collected among upper lateral veins and was ground in 96% alcohol, and the supernatant was subjected to measure on a spectrophotometer (Angilent 8453).</p><p><b>RESULT</b>The PPCs among cultivars were significantly different at a P < or = 0.01 level. The results of the measurements were similar. Chlolophyll a was the most abundant pigment, but varied to a great extent among different cultivars. 20 cultivars were divided into 9 homogeneous groups according to the contents of chlorophyll a by Duncan's multiple range test at P < or = 0.05. In addition, the content of chlorophyll a was closely related to leaf color. The cultivars with higher chlolophyll a had deep green leaves, and those with lower had yellow green or pale green leaves.</p><p><b>CONCLUSION</b>PPC was an inherent character and an important index for the germplasm evaluation of R. glutinosa.</p>