Andrographis paniculata and Its Bioactive Diterpenoids Against Inflammation and Oxidative Stress in Keratinocytes.

Andrographis paniculata was widely used in traditional herbal medicine to treat various diseases. This study explored the potential anti-aging activity of Andrographis paniculata in cutaneous cells. Human, adult, low calcium, high temperature (HaCaT) cells were treated with methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12). Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by fluorescence using a 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe and cytokines were quantified by ELISA for interleukin-8 (IL-8) or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for tumor necrosis factor-α (TNF-α). Hyaluronic acid (HA) secretion was determined by an ELISA. Our results show a decrease in ROS production and TNF-α expression by ME (5 µg/mL) in HaCaT under pro-oxidant and pro-inflammatory conditions, respectively. ME protected HaCaT against oxidative stress and inflammation. Our findings confirm that ME can be used for the development of bioactive compounds against epidermal damage.

Andrographis Paniculata and Its Bioactive Diterpenoids Protect Dermal Fibroblasts Against Inflammation and Oxidative Stress.

Andrographis paniculata (Burm.f.) has long been used in ayurvedic medicine through its anti-inflammatory properties. However, its protective effect of skin aging has not been studied in vitro. This study aimed to investigate the anti-aging effects of methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12) on human dermal fibroblasts (HDFa) under pro-oxidant or pro-inflammatory condition. The in vitro anti-aging capacity of ME, ANDRO, NEO, 14DAP, and 14DAP11-12 (1, 2.5 and 5 µg/mL) was performed in HDFa. Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by the fluorescence of DCF-DA probe and cytokines were quantified by ELISA (IL6 and IL8) or RTqPCR (TNF-α). Procollagen type I production was determined by an ELISA. Our results showed a decrease in ROS production with ME and 14DAP at 5 µg/mL and 1 µg/mL, respectively. Furthermore, IL-6 production and TNF-α expression decreased under ANDRO and ME at 5 µg/mL. Our data indicated that ME and 14DAP protect from oxidative stress. Additionally, ME and ANDRO decreased an inflammation marker, IL-6. This suggests their potential natural treatment against skin damage. Hence, their applications could be of interest in cosmetics for preventing skin ageing.

Andrographolide, a Natural Antioxidant: An Update.

Traditionally, Andrographis paniculata has been used as an herbal remedy for lung infection treatments. Its leaves contain a diterpenoid labdane called andrographolide responsible for a wide range of biological activities such as antioxidant, anti-inflammatory, and anti-cancer properties. This manuscript is a brief review of the antioxidant mechanisms and the regulation of the Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling pathway by andrographolide.

miR-181a modulates acute myeloid leukemia susceptibility to natural killer cells.

Although daunorubicin (DNR) is the most widely used anthracycline to treat acute myeloid leukemia (AML), resistance to this drug remains a critical problem. The aim of this study was to investigate the relationship between AML resistance to daunorubicin and susceptibility to natural killer (NK) cell-mediated cell lysis, and the putative expression of miRs. For this purpose, we used the parental AML cell lines U-937 and KG-1 and their equivalent resistant U937(R) and KG-1(R) cell lines. We demonstrate for the first time that the acquisition of resistance to DNR by the parental cell lines resulted in the acquisition of cross-resistance to NK cell-mediated cytotoxicity. miR microarray analysis revealed that this cross-resistance was associated with miR-181a downregulation and the subsequent regulation of MAP3K10 and MAP2K1 tyrosine kinases and the BCL-2 (BCL-2 and MCL-1) family. Overexpression of miR-181a in AML blasts resulted in the attenuation of their resistance to DNR and to NK-cell-mediated killing. These data point to a determinant role of miR-181a in the sensitization of leukemic resistant cells to DNR and NK cells and suggest that miR-181a may provide a promising option for the treatment of immuno- and chemo-resistant blasts.

Expression of two parental imprinted miRNAs improves the risk stratification of neuroblastoma patients.

Age at diagnosis, stage, and MYCN amplification are the cornerstones of the risk-stratification score of neuroblastoma that enables defining patients at low- and high risk. Refinement of this stratification is needed to optimize standard treatment and to plan future clinical trials. We investigated whether two parental imprinted miRNAs (miR-487b and miR-516a-5p) may lead to a risk score with a better discrimination. Expression levels of maternal miR-487b and paternal miR-516a-5p were determined using quantitative RT-PCR both for 231 neuroblastoma tumors (derivation set) and 101 independent neuroblastoma tumors (validation set). Survival outcomes were overall survival (OS) and disease-free survival (DFS). Multivariable Cox models were developed from derivation set and their performance evaluated using Akaike's information criterion (AIC) (goodness-of-fit) and time-dependent area under curves (discrimination). The selected model was validated using internal and external validation. The prognostic model including current prognostic factors plus miR-487b, miR-516a-5p, and interaction between two miRNAs was selected. Performance of this model was better in terms of both predictive ability (smallest AIC) and discrimination power (AUC close to 0.70). This model identifies three risk groups: high (3), intermediate (2), and low (1). Hazard ratios (HR) across risk groups were HR2/1 = 6.3 (2.7-14.6), HR3/1 = 14.8 (7.2-30.2) for OS and HR2/1 = 2.8 (1.5-5.4), HR3/1 = 7.2 (3.9-13.4) for DFS. The rank between these three risk groups was maintained and validated when performing internal and external validation. Expression of maternal miR-487b and paternal miR-516a-5p improves the risk stratification. This better discrimination at diagnosis is of clinical utility both for current and future treatments of neuroblastoma patients.