Panax notoginseng saponin R1 attenuates allergic rhinitis through AMPK/Drp1 mediated mitochondrial fission.

We investigated whether Panax notoginseng saponin (PNS-R1) attenuates allergic rhinitis (AR) through AMPK/Drp1-mediated mitochondrial fission. AR model was established in mice by Ovalbumin (OVA). In vitro, human nasal epithelial cells (HNEpCs) were stimulated using recombinant human interleukin 13 (IL-13). PNS-R1 was administrated in vivo and in vitro. Then, HE staining of nasal tissue, ELISA detection of immunoglobulin E (IgE) and proinflammatory cytokine levels in serum and nasal lavage fluid, flow cytometry analysis of Th1/Th2 ratio and apoptosis, TUNEL staining, Western blot, detection of reactive oxygen species (ROS) and mitochondrial ROS, immunofluorescence analysis of Tom20 and mitochondrial fission protein Drp1 co-localization, and mitochondrial membrane potential detection, were performed. PNS-R1 attenuated allergic symptoms in AR mice, decreased OVA-specific IgE, IL-4, IL-6, IL-8, IL-13, and TNF-α levels, and restored the Th1/Th2 imbalance. Meanwhile, we found that PNS-R1 treatment significantly reduced apoptosis, ROS production, and co-localization of Tom20 and Drp1 in the nasal epithelium of AR mice. In vitro, we found that PNS-R1 upregulated mitochondrial membrane potential and reduced ROS and mitochondrial ROS production as well as Cleaved-caspase-3/9, Bax, Cyt-c, Apaf-1 expression and mitochondrial fission. Mechanistically, we found that PNS-R1 downregulated Drp1 phosphorylation (Ser 616) and Drp1 translocation in an AMPK-dependent manner, promoted MFN2 expression, and reduced TXNIP, NLRP3, Caspase-1, and IL-1ß expression. PNS-R1 may protect mitochondrial integrity by inhibiting AMPK/Drp1 and TXNIP/NLRP3 signaling pathway, thereby alleviating AR symptoms in mice. PNS-R1 may have great potential as a therapeutic agent for AR.

Access to the Brazilian agenda of the National Rural Water Supply and Sanitation Project (1985) / Inclusión en la agenda brasileña del Proyecto Nacional de Abastecimiento de Agua y Saneamiento Rural (1985) / A entrada na agenda brasileira do Projeto Nacional de Saneamento Rural (1985)

Abstract This article seeks to understand the circumstances that culminated in the formulation and implementation of the National Rural Water Supply and Sanitation Project (PNSR) in the 1980s, using the Multiple Streams Model as its theoretical reference. The results show that the theme's ascension to the government agenda stemmed from a conjuncture marked by intense transitions that contributed to opening a policy window. The struggle to guarantee social rights in the Brazilian re-democratization process; the activities of social movements like the grassroots public health movement; the large sanitary deficit and its consequences for public health; the joint involvement of institutions with considerable expertise like Economic and Social Planning Institute (IPEA), Public Health Special Service Foundation (FSESP) and Pan-American Health Organization (PAHO) and the availability of financial resources stemming from a partnership arrangement with the International Bank for Reconstruction and Development (IBRD) provided a favorable environment for the elaboration of the PNSR.

Resumen Este documento tiene como objetivo comprender las circunstancias que condujeron a la formulación e implementación, en la década de 1980, del Proyecto Nacional de Abastecimiento de Agua y Saneamiento Rural (PNSR), adoptando como marco teórico el modelo de flujos múltiples. Los resultados muestran que su ascenso a la agenda del gobierno se debe a una coyuntura marcada por intensas transiciones, que contribuyeron a la apertura de una ventana de oportunidad. La búsqueda de la garantía de los derechos sociales en el proceso de redemocratización brasileña; el desempeño de movimientos sociales, como el movimiento sanitario; el gran déficit de saneamiento y sus consecuencias en la salud pública; la participación conjunta de instituciones con experiencia, como el Instituto de Planificación Económica y Social (IPEA), la Fundación del Servicio Especial de Salud Pública (FSESP) y la Organización Panamericana de la Salud (OPS), y la disponibilidad de recursos financieros de una asociación con el Banco Internacional de Reconstrucción y Fomento (BIRF) proporcionó un entorno favorable para la elaboración del PNSR.

Resumo O presente artigo busca compreender as circunstâncias que culminaram na formulação e implementação, na década de 1980, do Projeto Nacional de Saneamento Rural (PNSR), adotando como marco teórico o Modelo de Múltiplos Fluxos. Os resultados evidenciam que sua ascensão à agenda governamental é decorrente de uma conjuntura marcada por intensas transições, que contribuíram para a abertura de uma janela de oportunidades. A busca pela garantia de direitos sociais no processo de redemocratização brasileiro; a atuação de movimentos sociais, como o movimento sanitarista; o grande déficit sanitário e suas consequências na saúde pública; o envolvimento conjunto de instituições com expertise, como o Instituto de Planejamento Econômico e Social (IPEA), a Fundação Serviço Especial de Saúde Pública (FSESP) e a Organização Pan-Americana de Saúde (OPAS) e a disponibilidade de recursos financeiros, provenientes de parceria com o Banco Internacional para Reconstrução e Desenvolvimento (BIRD), proporcionaram um ambiente favorável para a elaboração do PNSR.

PNS-R1 inhibits Dex-induced bronchial epithelial cells apoptosis in asthma through mitochondrial apoptotic pathway.

Dexamethasone (Dex) are widely used for the treatment of asthma. However, they may cause apoptosis of bronchial epithelial cells and delay the recovery of asthma. Therefore, it is an urgent problem to find effective drugs to reduce this side effects. Panax notoginseng saponins R1 (PNS-R1) is known to exhibit anti-oxidative and anti-apoptotic properties in many diseases. We aim to investigate whether PNS-R1 can reduce Dex-induced apoptosis in bronchial epithelial cells. In this study, the anti-apoptotic effects of PNS-R1 were investigated by conducting in vitro and in vivo. Annexin V-FITC/PI staining flow cytometry analysis and TUNEL assay were conducted to detect apoptotic cells. Mitochondrial membrane potential was detected by JC-1 analysis. Western blotting and immunohistochemical analysis were conducted to measure caspase3, Bcl-2, Bax, Cyt-c, Apaf-1, cleaved-caspase3 and cleaved-caspase9 levels in lung tissues and 16HBE cells. Our findings demonstrated that Dex could induce apoptosis of bronchial epithelial cells and upregulate caspase3 expression of lung tissues. Western blot showed that Dex increased Bax, Cyt-c, Apaf-1, cleaved-caspase9, cleaved-caspase3 expression and decreased Bcl-2 expression. PNS-R1 could suppress Dex-induced apoptosis of bronchial epithelial cells by inhibiting Bax, Cyt-c, Apaf-1, cleaved-caspase9, cleaved-caspase3 expression and upregulating Bcl-2 expression. Flow cytometry analysis showed PNS-R1 alleviated JC-1 positive cells induced by Dex in 16HBE cells. These results showed that PNS-R1 alleviated Dex-induced apoptosis in bronchial epithelial cells by inhibition of mitochondrial apoptosis pathway. Furthermore, our findings highlighted the potential use of PNS-R1 as an adjuvant drug to treat asthma.