Methanol Extract of Aerial Parts of Pavetta indica L. Enhances the Cytotoxic Effect of Doxorubicin and Induces Radiation Sensitization in MDA-MB-231 Triple-Negative Breast Cancer Cells.

Pavetta indica L. is used in traditional medicine for the treatment of various diseases including hemorrhoids, headache, urinary conditions, ulcerated nose, and dropsy. However, no study has evaluated the anticancer effect of P. indica L. In this study, we found that a methanol extract of the leaves and branches of P. indica L. (MEPI) caused cellcycle arrest at the sub-G1 phase and induced apoptosis, as indicated by the activation of caspase-8, -3, -7, and c-PARP. Western blotting revealed that MEPI significantly reduced the levels of markers of the epithelial-mesenchymal transition, such as Vimentin, Snail, Slug, and matrix metallopeptidase 9. Notably, the expression of multidrug resistance-associated protein 1 in triple negative breast cancer (TNBC) was significantly decreased by MEPI. Moreover, the co-treatment with MEPI and doxorubicin resulted in a synergistic reduction in cell viability. MEPI also induced radiation sensitization of TNBC cells. Gas chromatography-mass spectrometry analysis revealed that 5,6-dehydrokawain (DK) is the major constituent of MEPI. Interestingly, DK exerted significant anti-invasive and anti-metastatic effects. Our results provide a strong rationale for investigating the molecular mechanisms of action of MEPI in TNBC.

Annona squamosa L. leaves inhibit alpha-melanocyte-stimulating hormone (α-MSH) stimulated melanogenesis via p38 signaling pathway in B16F10 melanoma cells.

BACKGROUND: Annona squamosa L. is a branched shrub, which is believed to be originated from the America and West Indies. Fruits of this plant are commonly known as custard apple, sugar apple, or sweetsops. A number of studies have proven a range of biological activities associated with various parts of A. squamosa. AIMS: The main aim of the present investigation was to evaluate potential inhibitory effects of A. squamosa leaf extract (ALE) on melanogenesis and its underlying mechanisms in B16F10 murine melanoma cells. METHODS: Inhibitory effects of A. squamosa leaf extract (ALE) on melanogenesis were primarily assessed by determining melanin contents. Effects of ALE on tyrosinase activity and the expression of proteins associated with melanogenesis were then determined. GC-MS analysis was carried out to identify the phytochemical profile of A. squamosa leaf extract. RESULTS: Antimelanogenic effects of ALE were found to exert through the inhibition of melanocyte inducing transcription factor (MITF) and activation of p38. GC-MS analysis identified ent-kaur-16-en-19-ol, 18-oxokauran-17-yl acetate, and ß-sitosterol as major phytochemicals. CONCLUSION: To our knowledge, this is the first study on the antimelanogenic effects of A. squamosa leaves, rationalizing the use A. squamosa leaf extract as a natural depigmentation agent for the treatment of skin diseases and the development of cosmetic products with enhanced skin-lightening capabilities.

Anti­inflammatory role of Prunus persica L. Batsch methanol extract on lipopolysaccharide­stimulated glial cells.

Glial cells are the resident immune cells of the central nervous system. Reactive glial cells release inflammatory mediators that induce neurotoxicity or aggravate neurodegeneration. Regulation of glial activation is crucial for the initiation and progression of neuropathological conditions. Constituents of the peach tree (Prunus persica L. Batsch), which has a global distribution, have been found to exert therapeutic effects in pathological conditions, such as rashes, eczema and allergies. However, the therapeutic potential of its aerial parts (leaves, fruits and twigs) remains to be elucidated. The present study aimed to evaluate the anti­inflammatory role of P. persica methanol extract (PPB) on lipopolysaccharide (LPS)­stimulated glial cells. High­performance liquid chromatography coupled with tandem mass spectrometry analysis showed that PPB contained chlorogenic acid and catechin, which have antioxidant properties. Western blot and reverse transcription polymerase chain reaction results indicated that PPB reduced the transcription of various proinflammatory enzymes (nitric oxide synthase and cyclooxygenase­2) and cytokines [tumor necrosis factor­α, interleukin (IL)­1ß and IL­6] in LPS­stimulated BV2 cells. In addition, PPB inhibited the activation of NF­κB and various mitogen­activated protein kinases required for proinflammatory mediator transcription. Finally, nitrite measurement and immunocytochemistry results indicated that PPB also suppressed nitrite production and NF­κB translocation in LPS­stimulated primary astrocytes. Thus, PPB may be used as a potential therapeutic agent for neurodegenerative diseases and neurotoxicity via the suppression of glial cell activation.

The complete chloroplast genome sequence of a vulnerable legume species Dalbergia tonkinensis prain in Vietnam.

Dalbergia tonkinensis is a critically vulnerable tree species that is distributed in Vietnam and Hainan Island of China. The complete chloroplast genome sequence of D. tonkinensis was characterized using Illumina pair-end sequencing. The cpDNA is 156,086 bp in length and contains a pair of 25,720 bp inverted repeats, one large single copy region of 85,761 bp, and one small single copy region of 18,885 bp. It contains 131 genes including 86 protein-coding genes, 36 tRNAs, eight rRNAs, and one pseudogene. The overall G + C content of the whole genome is 36.1%. Phylogenetic analysis based on 35 chloroplast genomes of Papilionoideae including Cercis glabra (as an outgroup) indicates that all the species of the Dalbergioids sensu lato formed a monophyletic clade and D. tonkinensis formed a sister relationship with the D. hainanensis and D. odorifera group.

Ethnobotanical study on medicinal plants used by local Van Kieu ethnic people of Bac Huong Hoa nature reserve, Vietnam.

ETHNOPHARMACOLOGICAL RELEVANCE: The ethnobotanical survey was carried out in the Bac Huong Hoa Nature Reserve (BHHNR), Vietnam. The Van Kieu ethnic group, the inhabitant of Nature Reserve, is rich in knowledge about the medicinal plants found in the Nature Reserve. However, their knowledge is less documented. AIM OF THE STUDY: The present study was conducted to document the use of medicinal plants, plant parts used, mode of preparation and delivery by the ethnic group of Van Kieu. The study also aimed at comparing the information generated by this study with the previously published Dictionary of Vietnam Medicinal plants (DVM). MATERIALS AND METHODS: The information was collected through semi-structured and unstructured interviews. The interviews were conducted from April 2016 to March 2017. The number of informants involved in the survey was 93 belonging to age group of 20-81. Species Use-Reports (UR) were analyzed to determine the plant importance in the local and the Informant Consensus Factor (FIC). Local plant uses were listed and compared with the previously published data from Vietnam. RESULTS: Comprehensively 355 Use-Reports were documented in this study. A total of 111 medicinal plant species belonging to 102 genera and 46 families were reported. Out of 46 families, Euphorbiaceae (10 species), Compositae and Leguminosae (9 species each), Apocynaceae (7 species), Rutaceae and Rubiaceae (5 species each) were the dominant families. Leaves were the most frequently used plant part (43.1%) in the preparation of medicines. The most frequent preparation method was decoction (49%) while the oral route of administration (51%) was the most commonly mentioned mode of administration. Artocarpus heterophyllus Lam., Chromolaena odorata (L.) R.M.King & H.Rob., Blumea balsamifera (L.) DC., Psidium guajava L. and Catunaregam spinosa (Thunb.) Tirveng. were shown to be the most useful plants as indicated by their relatively high UR. Eight medicinal plants (7.21%) used by Van Kieu ethnic people have not been previously reported in DVM. CONCLUSION: The Van Kieu ethnic group holds valuable knowledge about uses of medicinal plant resources which is inherited through generations however this knowledge was not documented. The study highlights the need for documenting and publicizing the traditional medicinal knowledge which will provide basic data for further research and conservation.

Cytotoxic activities of Telectadium dongnaiense and its constituents by inhibition of the Wnt/ß-catenin signaling pathway.

BACKGROUND: Wnt/ß-catenin signaling pathway is a potential target for the treatment of human colon cancer. Thus, the inhibitory effects of various plant extracts on cell proliferation and Wnt signal transduction were evaluated to discover a Wnt signaling inhibitor. PURPOSE: The present study aimed to investigate the cytotoxicity involved in Wnt pathway of the MeOH extract from Telectadium dongnaiense bark (TDB) and to identify its bioactive constituents by bioassay-guided fractionation. METHODS: The sulforhodamine B-based proliferation assay and the ß-catenin/TCF-responsive reporter gene assay were employed as screening systems. The isolation and identification of compounds were elucidated on the basis of spectroscopic methods. Inhibitory effects on the expression levels of Wnt target genes were determined by real-time PCR and western blotting. RESULTS: The extract of TDB most strongly inhibited cell proliferation and TOPflash activity (IC50 = 1.5 and 2.0 µg/ml), which was correlated with its inhibitory effects on the expression of Wnt target genes. Three major compounds were isolated from bioactive fractions and were identified as 1,4-dicaffeoylquinic acid (1), quercetin 3-rutinoside (2), and periplocin (3). Only compound 3 showed anti-proliferative activity (IC50 = 0.06 µM) and exhibited Wnt signaling inhibitory effects in HCT116 colon cancer cells. CONCLUSIONS: This study contributes to understanding the cytotoxic properties of TDB extract and its constituents and provides a potent strategy for its further application.

Dipterocarpus obtusifolius attenuates the effects of lipopolysaccharide­induced inflammatory response in RAW264.7 macrophages.

Dipterocarpus obtusifolius has been traditionally used as a herbal medicine and is considered to have anticancer properties. The biological activity of D. obtusifolius in inflammation and the underlying mechanisms of its activity remain to be elucidated. The present study investigated the effects of D. obtusifolius methanolic extract (DOME) on lipopolysaccharide (LPS)­stimulated inflammation in RAW264.7 cells. The effects of DOME on the production of nitric oxide, prostaglandin E2 and pro­inflammatory cytokines were assessed by ELISA, western blot analysis and reverse transcription­quantitative polymerase chain reaction. It was demonstrated that expression of inducible nitric oxide synthase, cyclooxygenase­2, interleukin­1ß and tumor necrosis factor­α was suppressed by DOME in LPS­stimulated cells. Furthermore, treatment with DOME suppressed phosphorylation of mitogen activated protein kinase (MAPK) molecules, including extracellular signal­regulated kinase, c­Jun N­terminal kinase and p38 MAPK. Translocation of the nuclear factor­κB p65 subunit into the nucleus was additionally inhibited by DOME. Phosphorylation of MAPK promoter activity was inhibited by treatment with DOME, PD98059, SB202190 and SP600125. These results demonstrated that DOME inhibits LPS­induced inflammatory responses. Therefore, DOME may be a potential therapeutic approach for the treatment of inflammatory diseases.

Chemical constituents from Melicope pteleifolia leaves.

Five acetophenones bearing spiroketal-hexofuranoside rings, one di-C-glycosidic acetophenone and two benzopyrans, along with 16 known compounds were isolated from the leaves of Melicope pteleifolia. Structures of all the isolates were elucidated using extensive spectroscopic methods, including 1D, 2D-NMR and HRESIMS. All the isolates were also evaluated for their neuraminidase inhibitory activities against H1N1, H9N2, wild-type H1N1 and oseltamivir-resistant H1N1 (H274Y mutation) virus strains. Of the isolates, tamarixetin 3-robinobioside was found to exhibit the strongest enzymatic inhibition (IC50 24.93 ± 3.46, 23.19 ± 5.41, 26.67 ± 5.16 and 40.16 ± 4.50 µM, respectively). Selected candidates, kaempferol 3-robinobioside, kaempferol 3-O-ß-d-glucopyranosyl (1 â†’ 2)-α-d-xylopyranoside and tamarixetin 3-robinobioside, also showed moderate reductions in H1N1-induced cytopathic effects on MDCK cells.