Wheat phenolics suppress doxorubicin-induced cardiotoxicity via inhibition of oxidative stress, MAP kinase activation, NF-κB pathway, PI3K/Akt/mTOR impairment, and cardiac apoptosis

The present investigation has been undertaken to reveal the protective mechanism of polyphenolics extract of whole wheat grains (WWGPE), ferulic acid and apigenin against doxorubicin (Dox)-induced cardio-toxicity. WWGPE, apigenin, and ferulic acid exhibited concentration dependent cyto-protective effect against Dox (1 μM) in rat cardiomyocytes. Dox treatment significantly (p < 0.01) induced oxidative stress in the myocardial cells via excessive ROS production, increase in iNOS expression, NADPH oxidase activation, Nrf-2/HO-1 impairment, and inactivation of cellular redox defense system. In addition, Dox significantly (p < 0.01) activated MAP kinases, NF-κB, and apoptosis in cardiac cells; while, significant (p < 0.01) impairment in PI3K/Akt/mTOR signaling was observed in Dox-treated myocardial cells. On the other hand, WWGPE, apigenin, and ferulic acid significantly (p < 0.05–0.01) attenuated Dox-induced redox stress and oxidative stress-mediated signal transduction in myocardial cells. WWGPE, apigenin, and ferulic acid treatment also could significantly (p < 0.05–0.01) reinstate Dox-mediated changes in blood parameters in rats. Histological assessments were in agreement with the biochemical findings. Results showed that, WWGPE exhibited better cardio-protective effect over ferulic acid and apigenin, which may be due to the synergy between the comprising compounds and better oral bioavailability of dietary antioxidant molecules from whole phenolic extract

Cordyceps sinensis (yarsagumba): Pharmacological properties of a mushroom

Introduction: Yarsagumba (Cordyceps sinensis or Ophiocordyceps sinensis) is a fungus that parasitizes ghost moth larvae and produces a fruiting body prized as herbal medicine, belonging to the Ophiocordycipitaceae family. Cordyceps species are also known as traditional Chinese medicine (TCM) as it has wide applications in the pharmaceutical and health sectors. For thousands of years, Yarsagumba has been recognized in Nepal. It is one of the world's most promising medicinal mushrooms. Its unusual life cycle and wide range of medical applications piqued scientists' curiosity throughout the previous three decades. The purpose of this review is to compile information on Yarsagumba, including its history, cultivation, taxonomic characteristics, and many therapeutic uses, as well as phytochemical and pharmacological studies completed to date. Methods: Different sources and distribution of the fungus have been presented along with its life cycle, morphology, collection procedure, and history as traditional Chinese medicine. Various chemical constituents of the fungus have been presented in tabular form with their significance as nutrients and traditional medicine. Various pharmacological activities have also been presented in tabular form with their mechanism of action, which include antiasthmatic, antineoplastic, antibacterial, aphrodisiac, cardioprotective, anti-cancer, immunomodulator, etc. Different adulteration methods and standardization approaches have also been summarized. Results: This review summarizes various aspects of yarsagumba relevant to its uses as traditional Chinese medicine. Conclusion: Despite its scientific advancement, further research is needed, particularly in the design of dosage forms and analysis that will lead to the most effective use of this most expensive medicinal fungus

The protective role of probiotics in the mitigation of carbon tetrachloride (CCl4) induced hepatotoxicity

Carbon tetrachloride (CCl4) is one of the traditional hepatotoxicants. Chronic liver damage can result from long-term CCl4 treatment, which is also a well-known model for producing hepatotoxicity. After entering the body, CCl4 is activated by hepatic cytochrome P450 and produces unstable trichloromethyl and trichloromethyl peroxyl radicals. These two types of free radicals attack polyunsaturated fatty acids in biofilm phospholipids and cause lipid peroxidation events, which might finally result in hepatotoxicity. It has recently been investigated that probiotic microorganisms have been found to reduce the liver damage caused by experimentally induced CCl4 exposure. The current review aims to compile experimental research on probiotics' ability to protect the liver against CCl4-induced hepatotoxicity. Nine different types of probiotic microbes were found to significantly protect against CCl4-induced hepatotoxicity in experimental preclinical investigations. According to the findings of the preclinical research, probiotics may be able to lessen the effects of CCl4-induced hepatotoxicity

Enhanced rosmarinic acid biosynthesis in <i>Solenostemon scutellarioides</i> culture: a precursor-feeding strategy

<div><p>The aim of this study was to employ precursor-feeding strategy for the improved production of rosmarinic acid (RA) in <i>S</i><i>olenostemon</i><i> scutellarioides in vitro</i>. The cultures were fed with precursors, namely l-phenylalanine (Phe), l-tyrosine (Tyr) and cucumber juice (CJ), at different concentrations. Phe (100 mg L^− 1) and Tyr (400 mg L^− 1) caused ∼1.5- and 2.1-fold increase in RA accumulation within 48 h. CJ (50 mg L^− 1) feeding displayed highest RA content (∼1.6-fold) in 72 h. In this study, we focused on the function of individual precursor on key enzymes involved in RA biosynthesis. The phenylalanine ammonia lyase activity was significantly upregulated after Phe (100 mg L^− 1) feeding, while tyrosine aminotransferase and hydroxyphenylpyruvate reductase activities were improved with Tyr (400 mg L^− 1) treatment. However, rosmarinic acid synthase activity was significantly enhanced by all three precursors. In synergy study, Phe (100 mg L^− 1) + Tyr (400 mg L^− 1) could enhance (∼3.1-fold) RA biosynthesis within 48 h.</p></div

Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response

Background: Abroma augusta L. (Malvaceae) leaf is traditionally used to treat diabetes in India and Southern Asia. Therefore, current study was performed to evaluate the protective effect of defatted methanol extract of A. augusta leaves (AA) against type 2 diabetes mellitus (T2DM) and its associated nephropathy and cardiomyopathy in experimental rats. Methods: Antidiabetic activity of AA extracts (100 and 200 mg/kg, p.o.) was measured in streptozotocin-nicotinamide induced type 2 diabetic (T2D) rat. Fasting blood glucose level (at specific interval) and serum biochemical markers (after sacrifice) were measured. Redox status, transcription levels of signal proteins (NF-kappa B and PKCs), mitochondria dependent apoptotic pathway (Bad, Bcl-2, caspase cascade) and histological studies were performed in kidneys and hearts of controls and AA treated diabetic rats. Results: Phytochemical screening of extracts revealed the presence of taraxerol, flavonoids and phenolic compounds in the AA. T2D rats showed significantly (p < 0.01) elevated fasting blood glucose level. Alteration in serum lipid profile and release of membrane bound enzymes like lactate dehydrogenase and creatine kinase, which ensured the participation of hyperlipidemia and cell membrane disintegration in diabetic pathophysiology. T2DM caused alteration in the serum biochemical markers related to diabetic complications. T2DM altered the redox status, decreased the intracellular NAD and ATP concentrations in renal and myocardial tissues of experimental rats. Investigating the molecular mechanism, activation PKC isoforms was observed in the selected tissues. T2D rats also exhibited an up-regulation of NF-kappa B and increase in the concentrations of pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) in the renal and cardiac tissues. The activation of mitochondria dependent apoptotic pathway was observed in renal and myocardial tissues of the T2D rats. However, Oral administration of AA at the doses of 100 and 200 mg/kg body weight per day could reduce hyperglycemia, hyperlipidemia, membrane disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Histological studies also supported the protective characteristics of A

Natural Variation in Elicitation of Defense-Signaling Associates to Field Resistance Against the Spot Blotch Disease in Bread Wheat (Triticum aestivum L.)

Spot blotch, caused by the hemibiotropic fungus Bipolaris sorokiniana, is amongst the most damaging diseases of wheat. Still, natural variation in expression of biochemical traits that determine field resistance to spot blotch in wheat remain unaddressed. To understand how genotypic variations relate to metabolite profiles of the components of defense-signaling and the plant performance, as well as to discover novel sources of resistance against spot blotch, we have conducted field studies using 968 wheat genotypes at 5 geographical locations in South-Asia in 2 years. 46 genotypes were identified as resistant. Further, in independent confirmatory trials in subsequent 3 years, over 5 geographical locations, we re-characterized 55 genotypes for their resistance (above 46 along with Yangmai#6, a well characterized resistant genotype, and eight susceptible genotypes). We next determined time-dependent spot blotch-induced metabolite profiles of components of defense-signaling as well as levels of enzymatic components of defense pathway (such as salicylic acid (SA), phenolic acids, and redox components), and derived co-variation patterns with respect to resistance in these 55 genotypes. Spot blotch-induced SA accumulation was negatively correlated to disease progression. Amongst phenolic acids, syringic acid was most strongly inversely correlated to disease progression, indicating a defensive function, which was independently confirmed. Thus, exploring natural variation proved extremely useful in determining traits influencing phenotypic plasticity and adaptation to complex environments. Further, by overcoming environmental heterogeneity, our study identifies germplasm and biochemical traits that are deployable for spot blotch resistance in wheat along South-Asia

The Emerging Role of HDACs: Pathology and Therapeutic Targets in Diabetes Mellitus

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into four different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting novel interventional strategies for metabolic disorders/complications