Effect of Pinocembrin Isolated from Mexican Brown Propolis on Diabetic Nephropathy.

Propolis is a resinous beehive product that has been used worldwide in traditional medicine to prevent and treat colds, wounds, rheumatism, heart disease and diabetes. Diabetic nephropathy is the final stage of renal complications caused by diabetes and for its treatment there are few alternatives. The present study aimed to determine the chemical composition of three propolis samples collected in Chihuahua, Durango and Zacatecas and to evaluate the effect of pinocembrin in a model of diabetic nephropathy in vivo. Previous research demonstrated that propolis of Chihuahua possesses hypoglycemic and antioxidant activities. Two different schemes were assessed, preventive (before renal damage) and corrective (once renal damage is established). In the preventive scheme, pinocembrin treatment avoids death of the rats, improves lipid profile, glomerular filtration rate, urinary protein, avoid increases in urinary biomarkers, oxidative stress and glomerular basement membrane thickness. Whereas, in the corrective scheme, pinocembrin only improves lipid profile without showing improvement in any other parameters, even pinocembrin exacerbated the damage. In conclusion, pinocembrin ameliorates diabetic nephropathy when there is no kidney damage but when it is already present, pinocembrin accelerates kidney damage.

Phytochemical Constituents, Antioxidant, Cytotoxic, and Antimicrobial Activities of the Ethanolic Extract of Mexican Brown Propolis.

Propolis is a complex mixture of natural sticky and resinous components produced by honeybees from living plant exudates. Globally, research has been dedicated to studying the biological properties and chemical composition of propolis from various geographical and climatic regions. However, the chemical data and biological properties of Mexican brown propolis are scant. The antioxidant activity of the ethanolic extract of propolis (EEP) sample collected in México and the isolated compounds is described. Cytotoxic activity was evaluated in a central nervous system and cervical cancer cell lines. Cytotoxicity of EEP was evaluated in a C6 cell line and cervical cancer (HeLa, SiHa, and CasKi) measured by the 3-(3,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium (MTT) assay. The antibacterial activity was tested using the minimum inhibitory concentration (MIC) assay. Twelve known compounds were isolated and identified by nuclear magnetic resonance spectroscopy (NMR). Additionally, forty volatile compounds were identified by means of headspace-solid phase microextraction with gas chromatography and mass spectrometry time of flight analysis (HS-SPME/GC-MS-TOF). The main volatile compounds detected include nonanal (18.82%), α-pinene (12.45%), neryl alcohol (10.13%), and α-pinene (8.04%). EEP showed an anti-proliferative effect on glioma cells better than temozolomide, also decreased proliferation and viability in cervical cancer cells, but its effectiveness was lower compared to cisplatin.

Protection against renal ischemia and reperfusion injury by short-term time-restricted feeding involves the mitochondrial unfolded protein response.

Food restriction improves metabolic health and increases resistance to stress in experimental animals. However, most studies have focused on long-term dietary restriction protocols consisting of several weeks or months of limited food ingestion. Here it was investigated the impact of 2-h time-restricted feeding (TRF) for one week on stress resistance in a rat model of kidney injury induced by ischemia and reperfusion (IR). At baseline, TRF reduced blood glucose, increased ß-hydroxybutyrate and improved body composition in male Wistar rats. Importantly, implementing the one-week TRF schedule before ischemia significantly improved renal function, suppressed tubular injury, prevented the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and inhibited the development of interstitial fibrosis. These benefits were related to increased antioxidant protection, reduction in dynamin-related protein 1 (DRP1)-mediated mitochondrial fragmentation and modulation of the mitochondrial unfolded protein response (UPRmt). Specifically, preoperative TRF boosted the activation of the UPRmt in the acute phase after renal IR while promoted its resolution at the stage of fibrosis. Our study indicates that dietary preconditioning by short-term TRF improves the outcome of renal IR injury, and suggests that an optimal intervention that promotes kidney protection may not necessarily require adherence to restrictive diets for prolonged periods of time.

Mechanisms of Fasting-Mediated Protection against Renal Injury and Fibrosis Development after Ischemic Acute Kidney Injury.

Ischemia-reperfusion injury of the kidney may lead to renal fibrosis through a combination of several mechanisms. We recently demonstrated that fasting protects the rat kidney against oxidative stress and mitochondrial dysfunction in early acute kidney injury, and also against fibrosis development. Here we show that preoperative fasting preserves redox status and mitochondrial homeostasis at the chronic phase of damage after severe ischemia. Also, the protective effect of fasting coincides with the suppression of inflammation and endoplasmic reticulum stress, as well as the down-regulation of the mechanistic target of rapamycin (mTOR) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways in the fibrotic kidney. Our results demonstrate that fasting targets multiple pathophysiological mechanisms to prevent renal fibrosis and damage that results after renal ischemia-reperfusion injury.

Mexican propolis flavonoids affect photosynthesis and seedling growth.

As a continuous effort to find new natural products with potential herbicide activity, flavonoids acacetin (1), chrysin (2) and 4',7-dimethylnarangenin (3) were isolated from a propolis sample collected in the rural area of Mexico City and their effects on the photosynthesis light reactions and on the growth of Lolium perenne, Echinochloa crus-galli and Physalis ixocarpa seedlings were investigated. Acacetin (1) acted as an uncoupler by enhancing the electron transport under basal and phosphorylating conditions and the Mg(2+)-ATPase. Chrysin (2) at low concentrations behaved as an uncoupler and at concentrations up to 100 µM its behavior was as a Hill reaction inhibitor. Finally, 4',7-dimethylnarangenin (3) in a concentration-dependent manner behaved as a Hill reaction inhibitor. Flavonoids 2 and 3 inhibited the uncoupled photosystem II reaction measured from water to 2,5-dichloro-1,4-benzoquinone (DCBQ), and they did not inhibit the uncoupled partial reactions measured from water to sodium silicomolybdate (SiMo) and from diphenylcarbazide (DPC) to diclorophenol indophenol (DCPIP). These results indicated that chrysin and 4',7-dimethylnarangenin inhibited the acceptor side of PS II. The results were corroborated with fluorescence of chlorophyll a measurements. Flavonoids also showed activity on the growth of seedlings of Lolium perenne and Echinochloa crus-galli.