Chemopreventive and Antioxidant Activity of the Chamazulene‐Rich Essential Oil Obtained from Artemisia arborescens L. Growing on the Isle of La Maddalena,Sardinia, Italy

The essential oils of Artemisia arborescens growing in Sardinia (Italy), collected during three plant growth stages, i.e., from the vegetative stage to post‐blooming time, were characterized. Moreover, the in vitro antiproliferative and antioxidant activities of the oil isolated from aerial parts collected in February were evaluated. The essential oils belonged to the β‐thujone/chamazulene chemotype, notably with the highest amount of chamazulene (ca. 52%) ever detected up to now in the genus Artemisia and, in general, in essential oils. Quantitative variations in the oil composition were observed as the plant passes from the vegetative to the blooming stage. The oil was tested for its potential tumor cell growth‐inhibitory effect on T98G, MDA‐MB 435S, A375, and HCT116 human cell lines, using the MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assay. The highest activity was observed on A375 and HCT116 cell lines, with IC₅₀ values of 14 μg/ml. Moreover, the in vitro antioxidant and free radical‐scavenging assays revealed the oil to be an effective scavenger of the ABTS radical cation, with an activity comparable to that of Trolox^®. These results support the use of A. arborescens oil for the treatment of inflamed skin conditions. Finally, the composition of the polar fraction of the A. arborescens aerial parts was also examined, and the main component detected was 5‐O‐caffeoylquinic acid, which was identified for the first time in this plant.     

Functional proteomics reveals the protective effects of saffron ethanolic extract on hepatic ischemia‐reperfusion injury

Hepatic ischemia‐reperfusion (IR) injury is a common clinical problem and ROS may be a contributing factor on IR injury. The current study evaluates the potential protective effect of saffron ethanol extract (SEE) in a rat model upon hepatic IR injury. Caspases 3 and terminal deoxynucleotidyl transferase‐mediated dUTP biotin nick end labeling (TUNEL) results showed increased cell death in the IR samples; reversely, minor apoptosis was detected in the SEE/IR group. Pretreatment with SEE significantly restored the content of antioxidant enzymes (SOD1 and catalase) and remarkably inhibited the intracellular ROS concentration in terms of reducing p47phox translocation. Proteome tools revealed that 20 proteins were significantly modulated in protein intensity between IR and SEE/IR groups. Particularly, SEE administration could attenuate the carbonylation level of several chaperone proteins. Network analysis suggested that saffron extract could alleviate IR‐induced ER stress and protein ubiquitination, which finally lead to cell apoptosis. Taken together, SEE could reduce hepatic IR injury through modulating protein oxidation and our results might help to develop novel therapeutic strategies against ROS‐caused diseases.     

在小鼠心跳骤停期间应用中度低温对复苏后抗氧化物酶活性的影响

目的：低温在许多小鼠心跳骤停后复苏模型的研究中被证实是有效的。心跳骤停后释放的氧自由基是产生继发性损伤的一个重要机制。本研究旨在探索心跳骤停期间应用中度低温对复苏后抗氧化物酶活性的影响。方法：用氯化钾诱导8min心跳骤停。此实验分为常温心跳骤停组（NCA）、低温心跳骤停组（HCA）TL对照组。HCA组在心跳骤停5min后开始降温使核心温度维持在（30．0±1．0）℃。应用胸部按压和肾上腺素来复苏。在心跳骤停两组各选择三个时间点：复苏后1h、4h和24h。测量超氧化物歧化酶（SOD）和过氧化氢酶（CAT）在心脏和肝脏的活性。结果：实验动物在HCA组比常NCA组生存率高。HCA组比NCA组复苏时间明显延长。与NCA组相比,HCA组复苏后24h的SOD活性在肝脏表达明显降低。与NCA组相比,HCA组复苏后4h的CAT活性在肝脏表达显著增高。结论：在心跳骤停过程中,与正常体温相比,应用中度低温能够提高生存率。与正常体温相比较,在心跳骤停中期间应用中度低温不影响心脏的SOD与CAT活性,应用中度低温在肝脏可延迟性抑制SOD的活性并且短暂提高CAT活性。     

A new fused tetracyclic heterocyclic antioxidant from Serratia sp. PAMC 25557

A new fused tetracyclic heterocyclic compound, (4bR,10bR)-4b-hydroxy-10b,12-dihydrodibenzo[c,h][2,6]naphthyridine-5,11(4bH,6H)-dione (1), and a known compound, butyl 2-[(benzoyloxy)methyl]benzoate, spatozoate 2, were isolated from the broth culture of Serratia sp. PAMC 25557. The structure of 1 was determined by analyzing spectroscopic data. Compound 1 did not exhibit antimicrobial activity against Escherichia coli, Staphylococcus aureus, or Candida albicans. In addition, up to 100 μg/ml compound 1 did not show any toxicity against Artemia salina larvae. However, compound 1 showed DPPH free radical scavenging activity (IC₅₀ = 16.7 ± 0.34 μg/ml). This was the first report of spatozoate isolation from bacterial sources.     

Antibacterial and antioxidant activities of flavonoids from Lannea alata (Engl.) Engl. (Anacardiaceae)

Two new prenylated flavonoids, lanneaflavonol (1) and dihydrolanneaflavonol (2) together with the known compounds myricetin-3-O-α-rhamnopyranoside (myricitrin) (3) and myricetin-3-O-α-arabinofuranoside (betmidin) (4), lupeol (5) and sitosterol (6) were isolated from the roots of Lannea alata. Compounds 1–4 exhibited good antibacterial and radical scavenging activity with the glycosides 3 and 4 showing better antioxidant activity than the aglycones 1 and 2 and myricetin-3-O-α-arabinofuranoside (4) showing the best antimicrobial activity followed by the aglycones 1 and 2. Betmidin (4) with an arabinose moiety at the 3-O-position showed the best antibacterial activity against Gram-positive bacteria, followed by the prenylated dihydroflavonol (2), whilst the prenylated linear flavonol (1) showed limited activity against Gram-negative bacteria. The arabinofuranoside (4) followed by the rhamnopyranoside (3) showed the best antioxidant activity comparable to that of ascorbic acid. The biological activities justify the ethnomedicinal uses of the plant in the management of diseases associated with Gram-positive bacteria, such as being used to treat injuries and wounds.     

Isolation of hopane triterpenes and other constituents from Machaerium brasiliense vogel (Fabaceae)

Phytochemical study of Machaerium brasiliense leaves extract afforded three hopane triterpenes 3,4-seco-21β-H-hop-22 (29)-en-3-oic acid (1), hopenone B (2), hopene B (3). In addition, lupeol (4), stigmasterol (5), β-sitosterol (6), daucosterol (7), uracil (8), allantoin (9) and trans-4-hydroxy-N-methylproline (10) were isolated. The structures of these compounds were established based on spectroscopic data in comparison to those described in literature. Considering the chemotaxonomic relevance of the isolated compounds, this is the first report of triterpenes 1, 2 and 3 in Fabaceae family and compounds 7, 8 and 9 in the genus Machaerium. Besides, preliminary screening on antiproliferative and antioxidant activities was performed for MBEB and its fractions.     

Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment

Despite many advances and optimization in colon cancer treatment, tumor recurrence and metastases make the development of new therapies necessary. Colon cancer stem cells (CCSCs) are considered as the main triggering factor of cancer progression, recurrence, and metastasis. CCSCs as a result of accumulated genetic and epigenetic alterations and also complex interconnection with the tumor microenvironment (TME) can evolve and convert to full malignant cells. Mounting evidence suggests that in cancer therapy both CCSCs and non-CCSCs in TME have to be regarded to break through the limitation of current therapies. In this regard, stem cell capabilities of some non-CCSCs may arise inside the TME condition. Therefore, a deep knowledge of regulatory mechanisms, heterogeneity, specific markers, and signaling pathways of CCSCs and their interconnection with TME components is needed to improve the treatment of colorectal cancer and the patient's life quality. In this review, we address current different targeted therapeutic options that target cell surface markers and signaling pathways of CCSCs and other components of TME. Current challenges and future perspectives of colon cancer personalized therapy are also provided here. Taken together, based on the deep understanding of biology of CCSCs and using three-dimensional culture technologies, it can be possible to reach successful colon cancer eradication and improvise combination targeted therapies against CCSCs and TME.     

Comparative analysis of activities of vital defence enzymes during induction of resistance in pearl millet against downy mildew

Pearl millet [Pennisetum glaucum (L.) R. Br.] has the seventh largest annual production in the world giving it significant economic importance. Although generally well adapted to the growing conditions in arid and semi-arid regions, major constraints to yields are susceptibility to downy mildew disease caused by the oomycete Sclerospora graminicola (Sacc.) Schroet. Induction of resistance against downy mildew disease of pearl millet has been well established using various biotic and abiotic inducers. The present study demonstrated the comparative analysis of the involvement of the important defence enzymes like β-1,3-Glucanase, chitinase, phenylalanine ammonia-lyase (PAL), peroxidase (POX), polyphenol oxidase (PPO) and lipoxygenase (LOX) during induced systemic resistance (ISR) mediated by inducers like Benzo(1,2,3)-thiadiazole-7-carbothionic acid-S-methyl ester (BTH), Beta amino butyric acid (BABA), Chitosan and Cerebroside against pearl millet downy mildew disease. Native-PAGE showed six POX isozymes in all categories of uninoculated pearl millet seedlings and maximum intensity of bands was noticed in resistant seedlings. After inoculation in Cerebroside-treated seedlings, there were seven isoforms, POX-4 was not present in any other seedlings. Native-PAGE analysis showed the presence of five PPO isozymes in all categories of uninoculated pearl millet seedlings and after inoculation seven isoforms of PPO-7 were noticed, and the intensity of banding was more in resistant and Cerebroside-treated seedlings. The isoforms PPO-3 were present as an extra band after inoculation in all seedlings. Isoform PPO-7, though found in all seedlings, was very prominent in Chitosan- and Cerebroside-treated seedlings. β-1,3-Glucanase Native-PAGE analysis showed the presence of only one isozyme in all categories of uninoculated/inoculated pearl millet seedlings. Glu-1 isozyme was very prominent in all seedlings including resistant and susceptible seedlings. Among the induced resistant seedlings, highest intensity was observed in Cerebroside-treated seedlings. Native-PAGE analysis showed the presence of three LOX isozymes in all categories of uninoculated pearl millet seedlings, and the intensity of banding pattern was very low in BTH-treated seedlings. LOX-1 and LOX-2 were very prominent in resistant, Chitosan- and Cerebroside-treated seedlings. Upon inoculation, one extra band, LOX-3, was exclusively noticed in Cerebroside-treated seedlings. In inoculated seedlings, LOX-1, LOX-2 and LOX-4 were very prominent in Chitosan Cerebroside-treated seedlings compared to other seedlings.