Cytotoxic, apoptotic and anti-α-glucosidase activities of 3,4-di-O-caffeoyl quinic acid, an antioxidant isolated from the polyphenolic-rich extract of Elephantopus mollis Kunth.

The decoction of the whole plant of Elephantopus mollis Kunth. is traditionally consumed to treat various free radical-mediated diseases including cancer and diabetes. This study was initiated to determine whether the most effective antioxidant compound isolated from the whole plant of Elephantopus mollis can also contribute to its claimed traditional values as anticancer and antidiabetes agents. An active antiradical phenolic compound (3,4-di-O-caffeoyl quinic acid) was isolated from the methanol extract (with the highest in polyphenolic content) and their antioxidant activities were compared using four different assays, that are DPPH, FRAP, metal chelating, and β-carotene bleaching tests. The compound was also evaluated for its cytotoxic activity, apoptotic induction and anti-glucosidase efficacies using methylene blue, DeadEnd™ assay and α-glucosidase assays, respectively. The compound acted as a greater primary antioxidant than its methanol extract, by having higher ferric reducing activity (EC(50) 2.18±0.05 μg/ml), β-carotene bleaching activity (EC(50) 23.85±0.65 μg/ml) and DPPH scavenging activity (EC(50) 68.91±5.44μg/ml), whereas the methanol extract exhibited higher secondary antioxidant activity as a metal chelator with lower EC(50) value (49.39±3.68 μg/ml) than the compound. Cytotoxicity screening of this compound exhibited a remarkable dose-dependent inhibitory effect on NCI-H23 (human lung adenocarcinoma) cell lines (EC(50) 3.26±0.35 μg/ml) and was found to be apoptotic in nature based on a clear indication of DNA fragmentation. This compound also displayed a concentration-dependent α-glucosidase inhibition with EC(50) 241.80±14.29 μg/ml. The findings indicate the major role of 3,4-di-O-caffeoyl quinic acid to antioxidant capacities of Elephantopus mollis extracts. The compound also exerted apoptosis-mediated cytotoxicity and α-glucosidase inhibitory effects and is thus a promising non toxic agent in treating cancer and type 2 diabetes mellitus.

Ooi KL ，Muhammad TS ，Tan ML ，Sulaiman SF ... -  《-》

The antimicrobial, antioxidative, anti-inflammatory activity and cytotoxicity of different fractions of four South African Bauhinia species used traditionally to treat diarrhoea.

Many Bauhinia species, including those indigenous to South Africa, are used in traditional medicine across the world for treating ailments such as gastrointestinal tract (GIT) disorders, diabetes, infectious diseases and inflammation. Several relevant aspects of different fractions of leaf extracts of Bauhinia bowkeri (BAB), Bauhinia galpinii (BAG), Bauhinia petersiana (BAP), and Bauhinia variegata (BAV) used in South African traditional medicine to alleviate diarrhoea related symptoms were evaluated. The antioxidative activities of the extracts were determined using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS(+)) radical scavenging and ferric reducing antioxidant power (FRAP) methods. In vitro antimicrobial activities of the extracts were determined against bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis) and clinical isolates of the opportunistic fungal strains (Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans) using a serial dilution microplate method. The polyphenolic contents were quantified using standard methods, and anti-inflammatory activities of the crude extracts were determined using the cyclooxygenase and soybean 15-lipoxygenase enzyme inhibitory assays. The safety of the extracts was evaluated by determining the cytotoxicity against Vero cell lines. The acidified 70% acetone crude extract and their fractions had good antiradical potency against the DPPH and ABTS radicals. The methanol soluble portions of the butanol fractions were more potent (EC(50) ranges from 0.64 ± 0.05 to 1.51 ± 0.07 and 0.88 ± 0.18 to 1.49 ± 0.09 μg/ml against DPPH and ABTS radical respectively) compared to the standard, trolox and ascorbic acid (EC(50) ranges from 1.47 ± 0.24 to 1.70 ± 0.27 μg/ml) for both DPPH and ABTS. The crude extracts contained variable quantities of phenolic content. The crude extracts and their fractions had weak to good antimicrobial activities, inhibiting the growth of the organisms at concentrations ranging from 39 to 2500 μg/ml. The BAG crude extract and its fractions were the most active against the fungi (MICs ranging from 39 to 625 μg/ml) while the BAB extract and its fractions were the least active with the MICs ranging between 39 and 2500 μg/ml. Aspergillus fumigatus was the least susceptible fungus while Cryptococcus neoformans was the most susceptible. The phenolic-rich crude extracts of BAB, BAG, and BAP had moderate to good dose-dependent cyclooxygenase-1 enzyme inhibitory activity with inhibitions between 22.8% and 71.4%. The extracts were however, inactive against cyclooxygenase-2. The extracts had some level of cytotoxicity towards Vero cell lines, reducing cell viability to less than 10% at concentrations more than 50 μg/ml. The biological activities observed in Bauhinia species provide a scientific basis for the use of the plants in traditional medicines to treat diseases with multi-factorial pathogenesis such as diarrhoea, with each aspect of activity contributing to the ultimate therapeutic benefit of the plants. However, the use of the phenolic-rich extracts of these plants to treat diarrhoea or any other ailments in traditional medicine needs to be monitored closely because of potential toxic effects and selective inhibition of COX-1 with the associated GIT injury.

Ahmed AS ，Elgorashi EE ，Moodley N ，McGaw LJ ，Naidoo V ，Eloff JN ... -  《-》

Anti-inflammatory, antioxidant, anti-tyrosinase and phenolic contents of four Podocarpus species used in traditional medicine in South Africa.

Species of Podocarpus are used traditionally in their native areas for the treatment of fevers, asthma, coughs, cholera, chest complaints, arthritis, rheumatism, venereal diseases and distemper in dogs. To investigate the antioxidant, anti-inflammatory and anti-tyrosinase activities of four Podocarpus species, Podocarpus elongatus, Podocarpus falcatus, Podocarpus henkelii and Podocarpus latifolius, used in traditional medicine in South Africa. Phytochemical analysis to determine the phenolic contents was also carried out. DPPH, FRAP and β-carotene-linoleic acid assays were used to determine the antioxidant/radical scavenging activities of these species. Anti-inflammatory activity of these species was assayed against two cyclooxygenase enzymes (COX-1 and COX-2). Tyrosinase inhibition activity was analysed using the modified dopachrome method with l-DOPA as the substrate. Phenolics were quantitatively determined using spectrophotometric methods. Stems of Podocarpus latifolius exhibited the lowest EC(50) (0.84 μg/ml) inhibition against DPPH. The percentage antioxidant activity based on the bleaching rate of β-carotene ranged from 96% to 99%. High ferric reducing power was observed in all the extracts. For COX-1, the lowest EC(50) value was exhibited by stem extracts of Podocarpus elongatus (5.02 μg/ml) and leaf extract of Podocarpus latifolius showed the lowest EC(50) against COX-2 (5.13 μg/ml). All extracts inhibited tyrosinase activity in a dose-dependent manner with stem extract of Podocarpus elongatus being the most potent with an EC(50) value of 0.14 mg/ml. The total phenolic content ranged from 2.38 to 6.94 mg of GAE/g dry sample. The significant pharmacological activities observed support the use of these species in traditional medicine and may also be candidates in the search for modern pharmaceuticals in medicine, food and cosmetic industries.

Abdillahi HS ，Finnie JF ，Van Staden J 《-》

Elephantopus mollis Kunth extracts induce antiproliferation and apoptosis in human lung cancer and myeloid leukemia cells.

Elephantopus mollis Kunth (EM), which belongs to Asteraceae family, has been used as a folk medicine with diverse therapeutic properties. Previous studies reported that crude extracts of this plant could inhibit several cancer cell lines, including breast carcinoma MCF-7, liver carcinoma HepG2, colorectal carcinoma DLD-1, lung carcinoma NCI-H23, etc. AIM: In this study, the anticancer activity and associated molecular mechanism of EM which is distributed in Vietnam were investigated. The cytotoxicity of various EM extracts was evaluated on different cell lines by MTT assay. In addition, the effects of EM extracts on cell growth, cell morphology, nuclear morphology, caspase-3 activation, and mRNA expression levels of apoptosis-related genes were also examined. Our results demonstrated that ethyl acetate extract (EM-EA) caused proliferative inhibition and apoptotic induction towards A549 lung cancer cells (IC50 = 18.66 μg/ml, SI = 5.8) and HL60 leukemia cells (IC50 = 7.45 μg/ml, SI = 14.5) while petroleum ether extract (EM-PE) showed high toxicity to HL60 cell line (IC50 = 11.14 μg/ml, SI = 6.7). Notably, Raji lymphoma cells were also affected by these extracts (IC50 < 20 μg/ml, SI > 4), which has not been reported yet. Furthermore, mechanisms of EM extracts were elucidated. The significant downregulation of PCNA mRNA level induced by EM-EA/PE extracts contributed to the cell-growth restraint. EM-EA extract might activate apoptosis in A549 cells through both extrinsic and intrinsic signaling pathways by causing a 1.55-fold increase in BID, 3.65-fold increase in BAK and 3.11-fold decrease in BCL-2 expression level. Meanwhile, with EM-EA-extract treatment, HL60 cells might encounter P53-dependent apoptotic deaths. The combination of antiproliferation and apoptosis activation contributed to the high efficacy of EM extracts. These findings not only proved the anticancer potential of EM but also provided further insights into the mechanisms of EM extracts.

Bich Ngoc TT ，Hoai Nga NT ，My Trinh NT ，Thuoc TL ，Phuong Thao DT ... -  《-》

Evaluation of selected biological capacities of Baeckea frutescens.

Navanesan S ，Wahab NA ，Manickam S ，Sim KS ... -  《BMC Complementary and Alternative Medicine》