Ginsenoside Rg1 attenuates arsenic-induced mice nephrotoxicity via the activated HO-1/mTOR-associated apoptosis or autophagy signaling

Nephrotoxicity attributed to environmental arsenic exposure, has been recognized by animal experiments and populational survey over 30 years in China, given a significance of public health by preventing from the disorder of renal function and hispathological abnormality. Here, Ginsenoside Rg1 (Rg1) as the commercial bioactive product of ginseng, play a beneficial role via antioxidant, anti-inflammatory and anti-apoptotic effects, which is poorly understood in arsenic-induced nephrotoxicity. The present study applied animal experiments to explore the pharmacological effects of Rg1 on sodium arsenite (SA)-induced nephrotoxicity in mice. Results showed that SA exposure led to renal pathological damage, and induced renal oxidative stress and the elevated levels of apoptosis or autophagy-associated indices in kidney. Further, western-blotting results confirmed the upregulations of pro-apoptotic Bax or autophagic unc-51-like kinase-1 (ULK1) or LC3-B signal, and the downregulations of HO-1 or mTOR signal and autophagy substrate sequestosome 1 (p62/SQSTM1) in kidney. Significantly, the intervention with Rg1 alleviated arsenic-induced renal pathological damage and oxidative stress, and upregulated the levels of HO-1, mTOR and p62, while the levels of Bax, ULK1 or LC3-B downregulated in kidney. In conclusion, the intervention with Rg1 relieves arsenic-induced mice nephrotoxicity maybe involved in the regulation of HO-1/mTOR-related apoptotic or autophagic signaling.

Plasma levels of bigEndothelin-1 are associated with renal insufficiency and in-hospital mortality of immune thrombotic thrombocytopenic purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by severe deficiency of plasma ADAMTS13 activity. Despite advances in early diagnosis and management, the mortality rate of acute iTTP remains high in a large part of world where access to some of the most novel therapies is limited. To determine the role of plasma bigEndothelin-1 (bigET-1) or its bioactive product ET-1 as a biomarker and/or a pathogenic factor in acute iTTP, plasma levels of bigET-1 were determined using an immunoassay in patients with iTTP on admission and during remission, as well as in healthy controls; moreover, the biological effect of ET-1 in thrombus formation was determined by a microfluidic assay. We show that plasma levels of bigET-1 were dramatically increased in patients with acute iTTP on admission, which was significantly decreased during clinical response/remission; elevated admission levels of plasma bigET-1 were associated with low estimated glomerular filtration rate, the need for intensive care unit admission or intubation, and in-hospital mortality. Moreover, an addition of a bioactive product ET-1 to cultured endothelial cells in a microfluidic channel dramatically accelerated the rate of thrombus formation under arterial flow. Our results demonstrate for the first time a potential role of measuring plasma bigET-1 in patients with acute iTTP in assessing the disease severity and risk of in-hospital mortality, which may help stratify patients for a more aggressive monitoring and therapeutic strategy; also, the bioactive ET-1, derived from bigET-1, may result in acute renal injury in TTP patient, likely through its vasoconstriction and prothrombotic properties.

Humiria balsamifera extract inhibits nitric oxide and tumor necrosis factor production in LPS-stimulated macrophages

Humiria balsamifera is used in traditional medicine as anthelmintic, expectorant, to treat hepatitis, diarrhea, hemorrhoids; to cure chronic wounds; and to alleviate toothaches. This species occurs in Jurubatiba shoal, Rio de Janeiro state-Brazil, a rich region which offers a variety of promising bioactive product sources. The present study focuses on the chemical and pharmacological evaluation of H. balsamifera. The n-hexane, dichloromethane and ethyl acetate leaf fractions exhibited higher inhibitory potential on NO production. Friedelin (1), quercetin (2) and quercetin-3-α-O-arabinopyranoside (3) were isolated and characterized; the latter is described for the first time for H. balsamifera. Quercetin (2) showed the best inhibitory activity on NO production and moderate inhibition of TNF-α production. These results contribute to the knowledge of Humiria balsamifera as a source of anti-inflammatory compounds. Furthermore, the identification of the terpenes ß-amyrone, betulin, citronellol, eremophillene, dihydroactinolide and borneol, and the isolation of quercetin-3-α-O-arabinopyranoside are being reported for the first time for this species.

Mutanofactin promotes bacterial adhesion and biofilm formation of cariogenic Streptococcus mutans

Cariogenic Streptococcus mutans is known as a predominant etiological agent of dental caries due to its exceptional capacity in forming biofilms. From strains of S. mutans isolated from dental plaque, we here discover a polyketide/non-ribosomal peptide biosynthetic gene cluster, muf, which directly correlates with a strong biofilm-forming capability. We then identify the muf-associated bioactive product, mutanofactin-697 that contains a novel molecular scaffold, along with its biosynthetic logic. Further mode-of-action studies reveal mutanofactin-697 binds to S. mutans cells nonspecifically, increases bacterial hydrophobicity, and promotes bacterial adhesion and subsequent biofilm formation. Our findings provide the first example of a microbial secondary metabolite promoting biofilm formation via a physicochemical approach, highlighting the significance of secondary metabolism in mediating critical processes related to the development of dental caries.

Antihyperglycemic, Vasodilator, and Diuretic Activities of Microencapsulated Bioactive Product from Moringa stenopetala Leaves Extract

Moringa stenopetala has nutritional and medicinal values, which is widely used by the local communities. The study aimed to evaluate the antihyperglycemic, vasodilator, and diuretic activities of the microencapsulated bioactive product from M. stenopetala leaves extract. Microencapsulation of the extract was done by spray drying technique using maltodextrin and pectin as coating materials with the core: coating ratio of 1 : 6. Then, the antihyperglycemic, diuretic, and vasodilator activities were evaluated after the product was administered to experimental animals at different doses and compared with the control groups. There were no observed physical, behavioral, and physiological changes on the mice during the acute toxicity test. The results also indicated no toxicity signs and death occurrence in the experimental animals up to 5000 mg/kg administered dose. Therefore, microencapsulated M. stenopetala leaves extract does not produce adverse effects in experimental mice. The study also showed that the microencapsulated bioactive product exhibited significant antihyperglycemic, vasodilator, and diuretic activities as the doses increase. Therefore, the study showed that microencapsulated bioactive product has significant medicinal values. Further detailed studies are recommended on chronic toxicity tests and to understand the possible mechanism of actions on the antihyperglycemic, vasodilator, and diuretic activities of the microencapsulated product.

Improved Cordycepin Production by Cordyceps militaris KYL05 Using Casein Hydrolysate in Submerged Conditions

Cordycepin, a beneficial bioactive product specifically found in Cordyceps, has received attention in various bioindustrial applications such as in pharmaceuticals, functional foods, and cosmetics, due to its significant functions. However, low productivity of cordycepin is a barrier to commercialization. In this study, Cordyceps militaris was mutated by UV irradiation to improve the cordycepin production. The highest producer KYL05 strain was finally selected and its cordycepin production was increased about 1.5-fold compared to wild type. In addition, the effects of culture conditions were fundamentally investigated. Optimal conditions were as follows: pH 6, temperature of 25 °C, shaking speed of 150 rpm, and culture time of 6 days. Effects of medium component on cordycepin production were also investigated by using various carbon and nitrogen sources. It was found that glucose and casein hydrolysate (CH) were most effective as carbon and nitrogen sources in cordycepin production (2.3-fold improvement) with maximum cordycepin production of about 445 mg/L. In particular, production was significantly affected by CH. These results should be of value in improving the efficiency of mass production of cordycepin.

Far-Red Light Acclimation for Improved Mass Cultivation of Cyanobacteria

Improving mass cultivation of cyanobacteria is a goal for industrial biotechnology. In this study, the mass cultivation of the thermophilic cyanobacterium Chlorogloeopsis fritschii was assessed for biomass production under light-emitting diode white light (LEDWL), far-red light (FRL), and combined white light and far-red light (WLFRL) adaptation. The induction of chl f was confirmed at 24 h after the transfer of culture from LEDWL to FRL. Using combined light (WLFRL), chl f, a, and d, maintained the same level of concentration in comparison to FRL conditions. However, phycocyanin and xanthophylls (echinone, caloxanthin, myxoxanthin, nostoxanthin) concentration increased 2.7–4.7 times compared to LEDWL conditions. The productivity of culture was double under WLFRL compared with LEDWL conditions. No significant changes in lipid, protein, and carbohydrate concentrations were found in the two different light conditions. The results are important for informing on optimum biomass cultivation of this species for biomass production and bioactive product development.