Guarana (Paullinia cupana) Stimulates Mitochondrial Biogenesis in Mice Fed High-Fat Diet.

The aim of this study was to evaluate the effects of guarana on mitochondrial biogenesis in a high-fat diet (HFD)-fed mice. C57BL6J mice were divided in two groups: high-fat diet HFD and high-fat diet + guarana (HFD-GUA). Both groups received HFD and water ad libitum and the HFD-GUA group also received a daily gavage of guarana (1 g/kg weight). Body weight and food intake was measured weekly. Glycemic, triglyceride, and cholesterol levels were determined. VO2 and energy expenditure (EE) were determined by indirect calorimetry. Gene expression was evaluated by real-time PCR and protein content by western blotting. The HFD-GUA group presented lower body weight, subcutaneous, retroperitoneal, visceral, and epididyimal adipose tissue depots, and glycemic and triglyceride levels, with no change in food intake and cholesterol levels. Furthermore, the HFD-GUA group presented an increase in VO2 and basal energy expenditure (EE), as well as Pgc1α, Creb1, Ampka1, Nrf1, Nrf2, and Sirt1 expression in the muscle and brown adipose tissue. In addition, the HFD-GUA group presented an increase in mtDNA (mitochondrial deoxyribonucleic acid) content in the muscle when compared to the HFD group. Thus, our data showed that guarana leads to an increase in energetic metabolism and stimulates mitochondrial biogenesis, contributing to control of weight gain, even when associated with high-fat diet.

Triptolide-induced hepatotoxicity can be alleviated when combined with Panax notoginseng saponins and Catapol.

ETHNOPHARMACOLOGICAL RELEVANCE: The hepatotoxicity of Tripterygium wilfordii Hook. f. (TW), due to the presence of triptolide (TP), limits its therapeutic potential. Based on the traditional Chinese medicine theory, the theory of "Yi lei xiang zhi" was proposed that Chinese herbs with different efficacy can restrict each other to achieve the least adverse reactions. AIM OF THE STUDY: To observe the effects of Catapol (CAT) and Panax notoginseng saponins (PNS), active ingredients in Rehmannia glutinosa (RG) and Panax notoginseng (PN) respectively, on reducing TP-induced hepatotoxicity, and further to explore the mechanisms. MATERIALS AND METHODS: The human hepatic cell line L-02 was cultured and treated with CAT, PNS or Combinations, and then treated with TP. The cytotoxic assay, the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), apoptosis, mitochondrial membrane potential and the expressions of NF-E2-related factor 1 (Nrf1) and its downstream targets were detected. Rats were treated with TP, TP + CAT, TP + PNS, or the combinations for 4 weeks. The levels of ALT, AST and LDH in serum, apoptosis of liver cells, mitochondria injury and the protein expressions of Caspase 3 and Nrf1 were investigated. RESULTS: CAT, PNS or CAT+PNS pre-treatment inhibited TP-induced toxicity in L-02 cells, distinctly decreased the apoptosis, alleviated the reduction of mitochondrial membrane potential, and modulated the expressions of Nrf1 and its downstream target, the mitochondrial transcription factor A (TFAM) and cytochrome C (Cyt-C). CAT, PNS or CAT+PNS inhibited the TP-induced hepatotoxicity in SD rats by reducing the mitochondria injury, decreasing the cells apoptosis and increasing the Nrf1 protein expression. Noticeably, TP + PNS + CAT combinations exhibited more effective than any single ingredient alone. CONCLUSION: PNS and CAT were able to effectively attenuate TP-induced hepatotoxicity. The efficiency benefits from their modulating Nrf1 and its downstream genes TFAM and Cyt-C, and further influencing mitochondrial functions and cells apoptosis. The combination is more effective than single ingredient alone.

Long-term intake of white tea prevents oxidative damage caused by adriamycin in kidney of rats.

BACKGROUND: White tea infusion (Camelia sinensis) has antioxidants properties. The infusion contains polyphenols that have been proposed to induce antioxidant response element (ARE) response via nuclear factor E2-related factor 2 (NRF2). Adriamycin (ADR) has antitumour properties and oxidative effects. Oxidative stress is related to a variety of kidney diseases. Prevention of the oxidative stress through long-term intake of white tea and the study of the molecular mechanisms involved in protection could be of great interest. Rats were given distilled water, 0.015 or 0.045 g of solid white tea extract kg(-1) body weight for 12 months. Animals received an injection of ADR. In kidney, oxidative stress parameters were measured, the expressions of nuclear factor E2-related factor 2 gene (Nrf2), and detoxifying and antioxidants genes were analysed, and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) were measured. RESULTS: ADR administration increased oxidative parameters and decreased the antioxidant activity; significantly increased the expression of analysed genes and the activity of CAT and SOD and decreased GR activity. The highest white tea dose protected redox status and inhibited ARE response. CONCLUSION: Long-term intake of white tea protected kidney against the oxidative stress. ADR activated the ARE response but in animals treated with the highest dose of white tea, this response was inhibited, probably for antioxidant protection. © 2015 Society of Chemical Industry.

Dietary isoflavone daidzein promotes Tfam expression that increases mitochondrial biogenesis in C2C12 muscle cells.

Mitochondrial dysfunction in muscles leads to a wide range of metabolic and age-related disorders. Recently, it has been reported that a natural polyphenol, resveratrol, affects mitochondrial biogenesis. This study aimed to identify other natural polyphenolic compounds that regulate mitochondrial biogenesis in muscles. For this purpose, we used the C2C12 murine muscle cell line. Screening involved a reporter assay based on the promoter of mitochondrial transcription factor A (Tfam). We found that several polyphenols exhibited the ability to increase Tfam promoter activity and that the soy isoflavone daidzein was a most potent candidate that regulated mitochondrial biogenesis. When C2C12 myotubes were treated with 25-50 µM daidzein for 24h, there were significant increases in the expression of Tfam and mitochondrial genes such as COX1 and Cytb as well as the mitochondrial content. Using several mutant Tfam promoter fragments, we found that the transcription factor, nuclear respiratory factor (NRF) and its coactivator, PGC1α, were necessary for the effect of daidzein on Tfam expression. Finally, silencing of sirtuin-1 (SIRT1) by shRNA resulted in inhibition of the daidzein effects on mitochondrial gene expression. In conclusion, daidzein regulates mitochondrial biogenesis in muscle cells by regulating transcriptional networks through a SIRT1-associated pathway. These results suggest that daidzein would be beneficial to protect against a wide range of diseases caused by muscle mitochondrial dysfunction.

Selenium supplementation induces mitochondrial biogenesis in trophoblasts.

INTRODUCTION: Placental oxidative stress has been implicated in pregnancy complications and previous work has shown that selenium can protect trophoblast mitochondria from oxidative stress. This report examines mitochondrial function and content in trophoblasts supplemented with selenium. METHODS: Swan-71, JEG-3 and BeWo cells and placental tissue were incubated with sodium selenite or selenomethionine. Mitochondrial function was examined in a respirometer. Mitochondrial content was determined using RT-PCR. The levels of the mitochondrial biogenesis markers selenoprotein H, PGC-1α and NRF-1 was examined by western blotting. RESULTS: Mitochondrial respiration was significantly enhanced post selenium supplementation in cells and tissues. Selenium supplementation increased mitochondrial content and up-regulated mitochondrial biogenesis mediators in cells. DISCUSSION: These results emphasise the importance of selenium in mitochondrial regeneration in trophoblasts.

Zinc protects cyclophosphamide-induced testicular damage in rat: involvement of metallothionein, tesmin and Nrf2.

The role of zinc (Zn) in the protection of germ cells against testicular toxicants has long been elucidated, but the exact molecular mechanisms have not yet been explored. Cyclophosphamide (CP), one of the most commonly used anticancer drugs survived ages of treatment, but the unwanted toxicity limits its clinical usage. The present investigation was aimed to explore the role of Zn and its associated pathways in CP-induced testicular toxicity in S.D. rat. CP was administered in saline 30 mg/kg 5× weekly for 3 weeks (total dose of 450 mg/kg) by i.p. route, while Zn was supplemented by oral route at the doses of 1, 3, 10mg/kg/day for 3 weeks. CP significantly reduced Zn levels in serum and testes, body and testicular weight, sperm count and motility, spermiogenic cells, plasma testosterone and significantly increased the oxidative stress, sperm head abnormalities, sperm DNA damage with decreased chromatin and acrosome integrity; while Zn supplementation ameliorated the same. The present results demonstrated that Zn supplementation protected against CP-induced testicular damages by modulating metallothionein (MT), tesmin and Nrf2 associated pathways. Thus Zn supplementation during anticancer therapy might be potentially beneficial in reducing the off target effects associated with oxidative stress.

Carthami Flos suppresses neutrophilic lung inflammation in mice, for which nuclear factor-erythroid 2-related factor-1 is required.

Carthami Flos (CF) is used in traditional Asian medicine to treat blood stagnation and its associated diseases in patients. While the underlying mechanism for this effect remains unknown, CF has been reported to activate Nrf2, a transcription factor that is critical in protecting from various inflammatory lung diseases including acute lung injury (ALI). Here, we examined whether CF has a therapeutic effect on lung inflammation and assessed the impact of Nrf2 on the effect of CF using an ALI mouse model. Treatment of bone marrow derived macrophages with standardized aqueous extract of CF (AECF) activated Nrf2, resulting in the expression of Nrf2 dependent genes including GCLC, NQO-1 and HO-1. While intranasal LPS treatment of wild type mice resulted in neutrophilic infiltration and a concomitant expression of pro-inflammatory cytokine genes in the lung, the hallmarks of ALI, an intratracheal spraying of AECF to the lung 2h after LPS treatment suppressed the inflammatory response. By contrast, similar treatment in nrf2(-/-) mice with AECF failed to attenuate the inflammatory response. Thus, our results show that AECF attenuated neutrophilic lung inflammation in mice, which required Nrf2. Since AECF administration abrogates lung inflammation after LPS treatment, we propose CF as a potential therapeutics in the management of ALI.

Stevioside induced ROS-mediated apoptosis through mitochondrial pathway in human breast cancer cell line MCF-7.

Stevioside is a diterpene glycoside found in the leaf of Stevia rebaudiana, a traditional oriental medicinal herb, which has been shown to have various biological and ethno-medicinal activities including antitumor activity. In this study, we investigated the effects of stevioside on the cytotoxicity, induction of apoptosis, and the putative pathways of its action in human breast cancer cells (MCF-7). For the analysis of apoptotic pathway, measurement of reactive oxygen species (ROS) and assessment of mitochondrial transmembrane potential (MTP) were achieved. We showed that stevioside was a potent inducer of apoptosis and it conveyed the apoptotic signal via intracellular ROS generation; thereby inducing change in MTP and induction of mitochondrial mediated apoptotic pathway. Taken together, our data indicated that stevioside induces the ROS-mediated mitochondrial permeability transition and results in the increased expression of apoptotic proteins such as Bax, Bcl-2 and Caspase-9. Effect of stevioside on stress-related transcription factors like NF-E2-related factor-2 opens up a new vista for further studies. This is the first report on the mechanism of the antibreast cancer (in vitro) activity of stevioside.