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A wide range of protein and polysaccharide structures have been applied for the encapsulation of bioactive compounds. In this research, a hydrogel was prepared using mung bean protein isolate and κ-carrageenan as a copolymer. The obtained hydrogel was used for encapsulating propolis at 1 % and 3 % (w/v). The rheological properties and the elasticity of the hydrogel samples with different percentages of propolis was investigated to determine resilience of the hydrogel. The textural analysis illustrated that propolis encapsulation does not change the hydrogel's chewiness, adhesiveness, and hardness. Fluorescence spectroscopy, FTIR, and SDS-PAGE techniques were used to determine the interactions between κ-carrageenan and mung bean protein isolate. The results suggested that electrostatic interactions and covalent bindings are responsible for gel preparation. Hydrophobic interactions contributed to propolis encapsulation. The quenching of aromatic amino acid residue and the clear propolis peak observed in fluorescence spectroscopy represented the role of hydrophobic interactions in encapsulation and gel formation. The water holding capacity (WHC) of >99 % and syneresis of <0.03 % of κ-carrageenan and mung bean protein isolate hydrogel represented an efficient structure of the hydrogel. The peak shifts of κ-carrageenan and mung bean protein isolates illustrated in the FTIR spectra were in line with SDS-PAGE results and fluorescence spectroscopy. The significantly increased encapsulation efficiency of >99 %, release rate of >50 %, and antioxidant activity of propolis encapsulated in κ-carrageenan and mung bean protein isolate suggested that the κ-carrageenan and mung bean protein isolate hydrogel is a potential delivery system and carrier for hydrophobic bioactive compounds, especially propolis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Obesity is a global epidemic that affects people of all ages, genders, and backgrounds. It can lead to a plethora of disorders, including diabetes mellitus, renal dysfunction, musculoskeletal problems, metabolic syndrome, cardiovascular, and neurodegenerative abnormalities. Obesity has also been linked to neurological diseases such as cognitive decline, dementia, and Alzheimer's disease (AD), caused by oxidative stress, pro-inflammatory cytokines, and the production of reactive oxygen free radicals (ROS). Secretion of insulin hormone is impaired in obese people, leading to hyperglycaemia and increased accumulation of amyloid-β in the brain. Acetylcholine, a key neurotransmitter necessary for forming new neuronal connections in the brain, decreases in AD patients. To alleviate acetylcholine deficiency, researchers have proposed dietary interventions and adjuvant therapies that enhance the production of acetylcholine and assist in the management of AD patients. Such measures include dietary intervention with antioxidant and anti-inflammatory flavonoid-rich diets, which have been found to bind to tau receptors, reduce gliosis, and reduce neuroinflammatory markers in animal models. Furthermore, flavonoids like curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, and oleocanthal have shown to cause significant reductions in interleukin-1β, increase BDNF levels, stimulate hippocampal neurogenesis and synapse formation, and ultimately prevent the loss of neurons in the brain. Thus, flavonoid-rich nutraceuticals can be a potential cost-effective therapeutic option for treating obesity-induced AD, but further well-designed, randomized, and placebo-controlled clinical studies are needed to assess their optimal dosages, efficacy, and long-term safety of flavonoids in humans. The main objectives of this review are to underscore the therapeutic potential of different nutraceuticals containing flavonoids that can be added in the daily diet of AD patients to enhance acetylcholine and reduce neuronal inflammation in the brain., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Essential trace metals like zinc (Zn), iron (Fe), and copper (Cu) play an important physiological role in the metabolomics and healthy functioning of body organs, including the brain. However, abnormal accumulation of trace metals in the brain and dyshomeostasis in the different regions of the brain have emerged as contributing factors in neuronal degeneration, Aβ aggregation, and Tau formation. The link between these essential trace metal ions and the risk of AD has been widely studied, although the conclusions have been ambiguous. Despite the absence of evidence for any clinical benefit, therapeutic chelation is still hypothesized to be a therapeutic option for AD. Furthermore, the parameters like bioavailability, ability to cross the BBB, and chelation specificity must be taken into consideration while selecting a suitable chelation therapy. The data in this review summarizes that the primary intervention in AD is brain metal homeostasis along with brain metal scavenging. This review evaluates the impact of different trace metals (Cu, Zn, Fe) on normal brain functioning and their association with neurodegeneration in AD. Also, it investigates the therapeutic potential of metal chelators in the management of AD. An extensive literature search was carried out on the "Web of Science, PubMed, Science Direct, and Google Scholar" to investigate the effect of trace elements in neurological impairment and the role of metal chelators in AD. In addition, the current review highlights the advantages and limitations of chelation therapies and the difficulties involved in developing selective metal chelation therapy in AD patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Mungbean is a vital pulse crop in India that can thrive in dry-land conditions and is grown in three seasons, with the added benefit of being used as green manure due to its ability to fix atmospheric nitrogen. Recently, pod rot disease has emerged as a serious threat to mungbean cultivation in India., Methods: In this study, morpho-molecular identification of associated pathogens and the bio-efficacy of systemic and non-systemic fungicides as well as genotype screening was performed during the years 2019 and 2020. The pathogens associated with this disease were confirmed on the basis of morphological and molecular characterization. For the molecular characterization, the translation elongation factor 1-alpha (tef-1) gene sequences were amplified by using primers (EF1 and EF2)., Results: Under in vitro conditions, trifloxystrobin + tebuconazole 75% WG was found to be the most effective against Fusarium equiseti (ED 50 2.39 μg ml -1 ) and Fusarium chlamydosporum (ED 50 4.23 μg ml -1 ) causal agents of pod rot of mungbean. Under field conditions, three applications of trifloxystrobin + tebuconazole 75% WG at 0.07% as a foliar application at fortnightly intervals starting from the last week of July proved to be the most effective against pod rot disease on mungbean cultivars, i.e., ML 2056 and SML 668. To identify the potential resistance sources, 75 interspecific derivative and mutant lines of mungbean were screened for disease reaction to pod rot under natural epiphytotic conditions for the years 2019 and 2020. Genotypic differences were observed for resistance to pod rot disease. The study revealed that among the tested genotypes, ML 2524 exhibited resistance to pod rot disease, with a disease incidence of 15.62% and disease severity of 7.69%. In addition, 41 other genotypes were found to be moderately resistant (MR) to the disease., Conclusion: Altogether, the identified management options will offer an immediate solution to manage this disease under recent outbreak conditions and pave a path for futuristic disease management using identified resistant sources in breeding programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Buttar, Singh, Sirari, Anupam, Kaur, Kumar, Lal, Tiwari and Kumar.)

Dietary supplements (DS) and their purchase is often based on a consumer's personal choice and advertisements. The associated DS regulations, particularly in manufacturing and marketing, are far more flexible and permissive than that of the well-regulated prescription pharmaceuticals. However, the adverse health effects associated with the inadvertent use of mega-doses of DS are not well understood. The demand for DS, nutraceuticals, and herbal remedies has experienced an upswing during the past two to three decades, and global product sales have thrived. More so, the prevention of cardiometabolic syndrome (CMS) and related disorders like diabetes mellitus, obesity, hypertension, and serum lipid abnormalities, as well as of other noncommunicable diseases (NCDs), is of highest health care priority globally, since these disorders impose very high economic burdens on health care systems and society. In this review, we argue why DS could prevent cardiometabolic syndrome, by providing the potential benefits and risks associated with them, especially self-medication considering their intake by the public at large. Good manufacturing practices and quality control are absolutely necessary for the manufacture of DS products, and proper labeling is needed regarding the optimal dose schedules of various DS and bioactive ingredients. Specific examples are used to underscore the indications and dosage recommendations made for the marketing and promotion of fish oil, coenzyme Q10, and Mg-containing products for the prevention of cardiometabolic syndrome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Télessy, Buttar, Wilson and Okpala.)

The renin-angiotensin system (RAS) plays a pivotal role in blood pressure regulation. In some cases, this steering mechanism is affected by various deleterious factors (mainly via the overactivation of the RAS) causing cardiovascular damage, including coronary heart disease (CHD) that can ultimately lead to chronic heart failure (CHF). This not only causes cardiovascular disability and absenteeism from work but also imposes significant healthcare costs globally. The incidence of cardiovascular diseases has escalated exponentially over the years with the major outcome in the form of CHD, stroke, and CHF. The involvement of the RAS in various diseases has been extensively researched with significant limelight on CHD. The RAS may trigger a cascade of events that lead to atherosclerotic mayhem, which causes CHD and related aggravation by damaging the endothelial lining of blood vessels via various inflammatory and oxidative stress pathways. Although there are various diagnostic tests and treatments available in the market, there is a constant need for the development of procedures and therapeutic strategies that increase patient compliance and reduce the associated side effects. This review highlights the advances in the diagnostic and treatment domains for CHD, which would help in subjugating the side effects caused by conventional therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mehta, Kaur, Buttar, Bagabir, Bagabir, Bagabir, Haque, Tuli and Telessy.)

Dysregulation of epigenetic mechanisms have been depicted in several pathological consequence such as cancer. Different modes of epigenetic regulation (DNA methylation (hypomethylation or hypermethylation of promotor), histone modifications, abnormal expression of microRNAs (miRNAs), long non-coding RNAs, and small nucleolar RNAs), are discovered. Particularly, lncRNAs are known to exert pivot roles in different types of cancer including breast cancer. LncRNAs with oncogenic and tumour suppressive potential are reported. Differentially expressed lncRNAs contribute a remarkable role in the development of primary and acquired resistance for radiotherapy, endocrine therapy, immunotherapy, and targeted therapy. A wide range of molecular subtype specific lncRNAs have been assessed in breast cancer research. A number of studies have also shown that lncRNAs may be clinically used as non-invasive diagnostic biomarkers for early detection of breast cancer. Such molecular biomarkers have also been found in cancer stem cells of breast tumours. The objectives of the present review are to summarize the important roles of oncogenic and tumour suppressive lncRNAs for the early diagnosis of breast cancer, metastatic potential, and chemotherapy resistance across the molecular subtypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kashyap, Sharma, Goel, Buttar, Garg, Pal, Rajab and Shaikh.)

Both Stevens-johnson syndrome (SJS) and Toxic-epidermal necrolysis (TEN) are generally medication-induced pathological conditions that mostly affect the epidermis and mucus membranes. Nearly 1 to 2 patients per 1,000,000 population are affected annually with SJS and TEN, and sometimes these maladies can cause serious life-threatening events. The reported death rates for SJS range from 1 to 5%, and 25 to 35% for TEN. The mortality risk may even be higher among elderly patients, especially in those who are affected by a significant amount of epidermal detachment. More than 50% of TEN patients who survive the illness may experience long-term lower quality of life and lesser life expectancy. The clinical and histopathological conditions of SJS and TEN are characterized by mucocutaneous discomfort, haemorrhagic erosions, erythema, and occasionally severe epidermal separation that can turn into ulcerative patches and dermal necrosis. The relative difference between SJS and TEN is the degree of ulcerative skin detachment, making them two extremes of a spectrum of severe cutaneous adverse drug-induced reactions (cADRs). In the majority of cases, serious drug-related hypercreativities are considered the main cause of SJS & TEN; however, herpes simplex virus and Mycoplasma pneumoniae infections may also produce similar type clinical conditions. The aetiology of a lesser number of cases and their underlying causative factors remain unknown. Among the drugs with a 'greater likelihood' of causing TEN & SJS are carbamazepine (CBZ), trimethoprim-sulfamethoxazole, phenytoin, aminopenicillins, allopurinol, cephalosporins, sulphonamides, antibiotics, quinolones, phenobarbital, and NSAIDs of the oxicam variety. There is also a strong genetic link between the occurrence of SJS and IEN in the Han Chinese population. Such genetic association is based on the human leukocyte antigen (HLA-B*1502) and the co-administration of carbamazepine. The diagnosis of SJS is made mostly on the gross observations of clinical symptoms, and confirmed by the histopathological examination of dermal biopsies of the patients. The differential diagnoses consist of the exclusion of Pemphigus vulgaris, bullous pemphigoid, linear IgA dermatosis, paraneoplastic pemphigus, disseminated fixed bullous drug eruption, acute generalized exanthematous pustulosis (AGEP), and staphylococcal scalded skin syndrome (SSSS). The management of SJS & TEN is rather difficult and complicated, and there is sometimes a high risk of mortality in seriously inflicted patients. Urgent medical attention is needed for early diagnosis, estimation of the SCORTEN prognosis, identification and discontinuation of the causative agent as well as highdose injectable Ig therapeutic interventions along with specialized supportive care. Historical aspects, aetiology, mechanisms, and incidences of SJS and TEN are discussed. An update on the genetic occurrence of these medication-related hypersensitive ailments as well as different therapy options and management of patients is also provided., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Bovine colostrum supplementation has been suggested as a potential factor in reducing oxidative stress and inflammation. The primary objective of this study was to evaluate the effects of six months of bovine colostrum supplement intake (3.2 g; four capsules/day) in highly trained female athletes on changes in oxidative stress level, inflammation, and iron metabolism biomarkers after intense exercise. In this study, 20 trained female athletes were recruited. Participants were divided into two groups: 11 in the bovine colostrum (6-month supplementation) and 9 in the placebo group (6-month placebo supplementation). All participants completed an intense exercise test at the beginning of the experiment and after six months post-treatment. Blood samples were taken before, following exercise, and after 3 h recovery. Compared to the placebo group, the colostrum group showed a significant decrease in TBARS level (p< 0.01) at all time points, whereas a marked increase was observed in IL-6 (p < 0.01; pre-exercise) and SOD activity (p < 0.01), and transferrin (p < 0.01; rest period) and lactoferrin (p < 0.05; post-exercise) levels. The results suggested that 6-months of bovine colostrum supplementation is beneficial in the reduction of the harmful effects produced by free radicals (ROS), oxidative stress, and inflammation. In consequence, alleviation of the inflammatory response by bovine colostrum supplementation may also cause positive action on iron homeostasis in female athletes.

In addition to providing individualized, specific, and ample nutritional compounds, donkey milk (DM) offers immunological modulation during health and disease. Recently, DM has attracted major interest in preparing infant formulas due to its similarity to human milk in terms of high protein and lactose content and low-fat concentration. The antimicrobial, anti-inflammation, antioxidant, and hypo-allergenicity properties of DM in human infants are well-documented. The purpose of this review is to summarize the knowledge of studies done in characterizing the composition of DM, including bioactive macronutrient levels influenced by the lactation status. The manufacture of DM-based food products and promising therapeutic applications in humans will also be discussed. The beneficial health effects of DM have been extensively studied as a valuable alternative source to breast milk. DM has proven to be a suitable nutrient to relieve milk-related allergies in human infants as opposed to cow's milk. Factors that influence the levels of macronutrients in DM include lactation status, processing, and manufacturing techniques. A wide variety of dairy products have been prepared using DM, such as cheese, ice cream, milk powder, novel functional fermented beverages, and milk powder for infant formulas. The bioactive macromolecules of DM exhibit antibacterial, antiviral, and antifungal effects as well as hypo-allergenicity, anti-inflammation, and antioxidant properties., (Copyright © 2022. Published by Elsevier Inc.)

Background: Gut microbiota is considered to have a great impact on human health and disease. While it is widely recognized that the gut microbiota of healthy individuals differs from those with obesity, inflammatory bowel disease, metabolic syndrome, and other chronic diseases, the alterations of gut microbiota with physical activity are not fully understood. Accordingly, we performed this systematic review to address the question regarding the effects of mild and intense exercise on the gut microbiota in humans., Methods: The comparative analyses of gut microbiota were conducted following the PRISMA protocol to determine the differences in the active vs. non-active individuals (phenotypes) (n = 11), including the influence of physical activity intervention on the human gut microbiota (n = 13); the differences in the gut microbiota of athletes vs. non-athletes (n = 8); and the microbiota status at different stages of athletic performance or intervention (n = 7), with various of physical activities, sport disciplines, and activity duration. Literature searches were completed using four databases: PubMed, Web of Science, Scopus, and EBSCO, and 2090 articles were retrieved by using appropriate keywords. The low heterogeneity of the studies hasn't allowed us to prepare a meta-analysis. After excluding 2052 articles, we ultimately selected 38 articles that met the eligibility criteria for this review., Results: The data analyses revealed that in non-athletes rising physical activity markedly influenced the relative abundance of short-chain fatty acid (SCFA). Aerobic training that lasted 60 min, and physical activity that characterized 60% HRmax or more also influenced beta diversity indexes. The results showed that athletes harbor a more diverse type of intestinal microflora than non-athletes, but with a relatively reduced abundance of SCFA- and lactic acid-producing bacteria, thereby suggesting an adverse effect of intense exercise on the population of gut microbiota., Conclusion: It is concluded that the level of physical activity modulates the gastrointestinal microbiota in humans. For a long period, increasing the intensity and volume of exercise may lead to gut dysbiosis. Perhaps, proper supplementation should be considered to keep gut microbiota in large biodiversity and richness, especially under unfavorable gut conditions associated with intense exercise., Trial Registration: Prospero CRD42021264064., (© 2022. The Author(s).)

Background: Bovine colostrum (BC) contains a myriad of bioactive molecules that are renowned for possessing unique medicinal benefits in children and adults, and BC supplements are considered safe and cost-effective options to manage/prevent the incidence of upper respiratory tract infections and gut-related problems in athletes. In this review, we will try to answer the question: How will BC supplementation ameliorate gut permeability problems among athletes?, Methods: Literature searches were performed using PRISMA guidance to identify studies assessing the influence of BC supplements on gut permeability. Studies were selected using four databases: PubMed, Web of Science, Scopus, and EBSCO, and a total number of 60 articles were retrieved by using appropriate keywords., Results: Nine studies were selected that met the eligibility criteria for this review. The data analysis revealed that vigorous exercise profoundly increases intestinal permeability, and BC supplementation helps to reverse gut permeability in athletes., Conclusion: BC supplementation may be highly beneficial in improving gut permeability in athletes. However, well-designed, placebo-controlled, and randomized studies are needed to evaluate the long-term safety and efficacy and to determine the optimal dose schedules of BC supplementation in high-performance athletes.

4-(methylthio)butyl isothiocyanate (4-MTBITC) also called erucin is abundantly present in the seeds of Eruca sativa plant closely related to cruciferous vegetables rich in isothiocyanates. We have previously reported the molecular targets of 4-MTBITC, but no acute, subacute and subchronic toxicity studies have been carried out to evaluate its safety. The non-everted gut sac method was used to study intestinal absorption and it revealed the highest absorption of 4-MTBITC in the jejunum. Dose-dependent pharmacokinetic parameters were observed in rats given 10, 20, and 40 mg/kg oral doses of 4-MTBITC. At the highest dose of 40 mg/kg, C max was 437.33 μg/ml and T max was 30 min, suggesting quick absorption and delayed elimination with elimination constant, 0.0036 ± 0.0002min -1 . In a 14 days toxicity study, the mean LD 50 of 4-MTBITC was 500 mg/kg body weight. After 28 and 90 days of treatment with 4-MTBITC (2.5, 10, 40 mg/kg/day), significant increases were observed in SGOT, cholesterol, and antioxidant enzymes. The levels of glycine, alanine and lysine were markedly increased in the liver tissue, thereby indicating that the liver was the target organ of 4-MTBITC induced toxicity in female animals. The histopathological examination of liver, kidney, and lung tissues revealed little focal necrosis, apoptosis, and reduction in the levels of amino acids involved in cellular metabolic pathways, indicating the anti-proliferative potential of 4-MTBITC against rapidly growing cells., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bovine colostrum (BC) is the initial mammary secretion after parturition, which is nature's bountiful source consisting of nutritional and bioactive components present in a highly concentrated low-volume format. All mammalian newborns require colostrum to enhance physiological processes such as lifelong immunity, gastrointestinal development, and resistance to microbial infections. The genetic, environmental, and processing methods can all have an impact on the biochemical contents of BC and its supplements. BC and its derivatives have been intensively researched for their potential use in functional foods, medicines, and animal feed. Evidence from clinical studies suggests that BC products are well-tolerated, nontoxic, and safe for human ingestion. Functional foods, feed, and pharmaceutical formulations based on bovine colostrum are playing noteworthy roles in the development of innovative products for promoting health and the prevention of chronic illnesses. This systematic review sheds light on recent research on (a) the effects of processing techniques on BC components, (b) emerging techniques used in the isolation and identification of novel components, (c) BC-based functional foods for human consumption and animal feed supplements, and (d) the role of BC in current drug delivery, as well as future recommendations.

The overwhelming global burden of cancer has posed numerous challenges and opportunities for developing anti-cancer therapies. Phytochemicals have emerged as promising synergistic compounds with potential anti-cancer effects to supplement chemo- and immune-therapeutic regimens. Anti cancer synergistic effects have been investigated in the interaction between phytocompounds derived from flavonoids such as quercetin, apigenin, kaempferol, hesperidin, emodin, etc., and conventional drugs. Xanthohumol is one of the prenylated phytoflavonoid that has demonstrated key anti-cancer activities in in vitro (anti proliferation of cancer cell lines) and in vivo (animal models of xenograft tumours) studies, and has been explored from different dimensions for targeting cancer subtypes. In the last decade, xanthohumol has been investigated how it induces the anti- cancer effects at cellular and molecular levels. The different signalling cascades and targets of xanthohumol are summarized in this review. Overall, this review summarizes the current advances made in the field of natural compounds with special reference to xanthohumol and its promising anti-cancer effects to inhibit tumour progression. The present review has also discussedthe potential of xanthohumol transitioning into a leadingcandidate from nano-therapy viewpoint along with the challenges which need to be addressed for extensive preclinical and clinical anti-cancer studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Baicalein is a medicinally important flavonoid present in Scutellaria baicalensis , which has numerous biological benefits like anti-oxidant, anti-inflammatory, antihepatotoxicity, anticancer properties, etc. Recent studies have revealed that baicalein is an efficient antihepatoma agent and has the strongest antiproliferative effect toward cancerous bladder cell lines, and suppression of cell cycle progression in prostate cancer cells. This natural substance has a high commercial value because it strengthens the heart and cerebral vessels and protects the nervous system and also reduces diabetes and diabetic complications. In addition, baicalein is known to decrease inflammatory markers such as IL-1β, IL-6 and TNF-α. In this review, we have attempted to compile the list of recent therapeutic patents of baicalein used for treating different disorders.

Viral infections are posing a great threat to humanity for the last few years. Among these, Chikungunya which is a mosquito-borne viral infection has produced enormous epidemics around the world after been rebounded. Although this infection shows a low mortality rate, patients suffer from fever, arthralgia, and maculopapular rashes, which reduce the quality of life for several weeks to years. The currently available treatments only provide symptomatic relief based on analgesics, antipyretics, and anti-inflammatory drugs which are nonspecific without satisfactory results. Medicinal plants are a widely accepted source of new molecules for the treatment of infectious diseases including viral infections. The scientific reports, primarily focusing on the anti-chikungunya activity of plant extracts, natural origin pure compounds, and their synthetic analog published from 2011 to 2021, were selected from PubMed, Google Scholar, and Scopus by using related keywords like anti-chikungunya plants, natural antivirals for Chikungunya. The present review decodes scientific reports on medicinal plants against chikungunya virus (CHIKV) infection and demystifies the potential phytoconstituents which reveals that the screening of flavonoids containing plants and phytochemicals showing efficacy against other arbovirus infections, may prove as a potential lead for drug development against CHIKV. The present article also outlines pathogenesis, clinical aspects, molecular virology, and diagnostic approaches of CHIKV infection., Competing Interests: None

4-(methylthio)butyl isothiocyanate (4-MTBITC) is a hydrolytic product from the plant Eruca sativa Thell. In the present study, we explored the anti-cancer effect of 4-MTBITC against 7,12-dimethylbenz [a] anthracene (DMBA) induced breast cancer. Hypoxic conditions were developed using a single dose of 60 mg/kg DMBA. Hepatic and renal parameters were increased along with antioxidants in cancer-bearing rats which were lowered with the treatment of 4-MTBITC. Further, it inhibited the up-regulation of glycolytic enzymes caused by DMBA. The hypoxia pathway was evaluated using RT-PCR and it was found that the 40 mg/kg doses of 4-MTBITC statistically lowered the expression of HIF-1α. Akt/mTOR signaling pathway was one of the major pathways involved in 4-MTBITC-induced cell growth arrest by western blotting. Amino acid profiling serum-free plasma revealed the downregulation of specific amino acids required for vital components of fast-growing cancer cells. 4-MTBITC reduced the levels of serine, arginine, alanine, asparagines, and glutamic acid. Histological examination also showed neoplastic growth following DMBA doses. 4-MTBITC treated rats showed less infiltration and normal physiology. Our findings for the first time demonstrated the potential therapeutic significance of 4-MTBITC on modulation of glycolytic enzymes and hypoxia pathway in female rats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a past co-authorship with one of the authors (HSB)., (Copyright © 2021 Singh, Thakur, Singh, Buttar, Singh and Arora.)

Curdlan is an exopolysaccharide, which is composed of glucose linked with β-(1,3)-glycosidic bond and is produced by bacteria, such as Alcaligenes spp., Agrobacterium spp., Paenibacillus spp., Rhizobium spp., Saccharomyces cerevisiae, Candida spp., and fungal sources like Aureobasidium pullulan, Poria cocos , etc. Curdlan has been utilized in the food and pharmaceutical industries for its prebiotic, viscosifying, and water-holding properties for decades. Recently, the usefulness of curdlan has been further explored by the pharmaceutical industry for its potential therapeutic applications. Curdlan has exhibited immunoregulatory and antitumor activity in preclinical settings. It was observed that curdlan can prevent the proliferation of malarial merozoites in vivo ; therefore, it may be considered as a promising therapy for the treatment of end-stage malaria. In addition, curdlan has demonstrated potent antiviral effects against human immunodeficiency virus (HIV) and Aedes aegypti virus. It has been suggested that the virucidal properties of curdlans should be extended further for other deadly viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19). The prebiotic property of curdlan would confer beneficial effects on the host by promoting the growth of healthy microbiota in the gut and consequently help to reduce gastrointestinal disorders. Therefore, curdlan can be employed in the manufacture of prebiotics for the management of various gastrointestinal dysbiosis problems. Studies on the mechanism of action of curdlan-induced suppression in microbial and tumor cells at the cellular and molecular levels would not only enhance our understanding regarding the therapeutic effectiveness of curdlan but also help in the discovery of new drugs and dietary supplements. The primary focus of this review is to highlight the therapeutic interventions of curdlan as an anticancer, anti-malaria, antiviral, and antibacterial agent in humans. In addition, our review provides the latest information about the chemistry and biosynthesis of curdlan and its applications for making novel dairy products, functional foods, and nutraceuticals and also details about the recent patents of curdlan and its derivatives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chaudhari, Buttar, Bagwe-Parab, Tuli, Vora and Kaur.)

Cancer is a global multifactorial disease consisting of over 200 types of cancers. It is well recognized that primary prevention is an effective way to fight cancers by using natural polyphenolic anticancer foods, vegetables, and fruits, avoiding exposure to the carcinogenic environment, smoking cessation, and through lifestyle modifications. The present review provides up-todate information on the effects and functions of pomegranate juice and its bioactive components on the most widespread six cancer types. Pomegranate contains important polyphenolic compounds, such as ellagitannins and punicalagin, with strong antioxidant ability for scavenging free radicals and producing metal-chelates in the biological tissues. The in vitro and in vivo studies suggests that antioxidant and anti-inflammation properties of pomegranate constitute have major antimutagenic and antiproliferative activities for regulating gene expression, modulating cellular mechanisms, and limiting the ability of cancers to metastasize. A limited number of clinical studies have suggested that pomegranate ingredients have the potential for the prevention and treatment of cancer, especially colorectal and prostate cancer. In cancer therapy, it remains a clinical dilemma to hit the right target without inducing side effects. The costly anticancer chemotherapies are often associated with drug resistance and serious side effects in vital organs and noncancerous neighboring cells. It appears that the pomegranate-based phytotherapy would be affordable and cost-effective for next-generation non-pharmacologic anticancer remedies with lesser side effects. However, well-designed, randomized, double-blind, and multi-center studies are needed to establish the long-term safety, efficacy, and dose schedules for orally deliverable pomegranate formulations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Phyllanthusfraternus is a pantropical weed of family phyllanthaceae, mainly found in northeast India. It has been used in the folklore medicine of Manipur tribe for treating type 2 diabetes., Objective: The present study was commenced to evaluate the anti-diabetic and renoprotective potential of P.fraternus (aerial parts) in alloxan-induced diabetes in rats., Materials and Methods: Alloxan (130 mg/kg, ip) was used for the induction of diabetes in adult male wistar rats. Animals with blood glucose level greater than 280 mg/dL were treated once daily for 14 days with various test extracts. The biochemical parameters were measured from serum on the 15th day post-treatment. Necropsy samples harvested from pancreas and kidneys were examined for histopathological changes in these organs., Results: Alloxan-induced diabetes not only caused significant increases in blood glucose, triglycerides, total cholesterol, creatinine and urea levels, but also provoked high oxidative stress in pancreas and kidneys. Profound morphological injuries were observed in islets of Langerhans and kidneys of diabetic animals. Administration of methanol extract (200 and 400 mg/kg) and mother liquor (200 and 400 mg/kg) ameliorate the elevated levels of blood glucose, triglycerides, total cholesterol as well as other biochemical parameters, but highest reduction in blood glucose concentration was observed with the largest dose of ethyl acetate fraction (400 mg/kg) of P.fraternus. Histopathological examination of pancreas and kidneys also exhibited greater protection by treatment with acetate fraction (400 mg/kg). The HPLC analysis showed the presence of four polyphenols such as catechin, gallic acid, caffeic acid and ellagic acid in ethyl acetate fraction of P. fraternus during HPLC analysis., Conclusion: The results suggest that polyphenols present in P.fraternus may be responsible for the anti-diabetic and renoprotective activity in rats. Such protective effects of could be mediated through flavonol-induced anti-oxidant and anti-inflammatory activities in the pancreas and kidneys., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The incidence of gastrointestinal disorders (GID) and cancers is escalating all over the world. Limited consumption of colostrum by newborns not only weakens the immune system but also predisposes infants to microbial infections. Colostrum is nature's perfect food, sometimes referred to as the 'elixir of life'. Breast-fed infants have a lower incidence of GI tract infections than infants fed formula or cow's milk. As per WHO statistics, cancer is the most prevalent disease globally and causes 9.6 million deaths worldwide. The current strategies for treating cancer include chemotherapy, radiation, and surgery. However, chemotherapy and radiation exposure are usually associated with serious long-term side effects and deterioration in the quality of life (QOL) of patients. Furthermore, the hospitalization and medication costs for treating cancers are exorbitant and impose high economic burden on healthcare systems. People are desperately looking for cost-effective and affordable alternative therapies for treating GID and cancers. Therefore, there is an urgent need for clinically evaluating the anticancer compounds isolated from plants and animals. Such therapies would not only be economical and have fewer side effects, but also help to improve the QOL of cancer patients. Recently, bovine colostrum (BC) has caught the attention of many investigators to explore its anticancer potential in humans. BC impregnated dressings are highly effective in treating chronic wounds and diabetic foot ulcer. BC is rich in lactoferrin, a glycoprotein with strong antioxidant, anti-inflammatory, anti-cancer, and anti-microbial properties. Intravaginal application of BC tablets is effective in causing the regression of low-grade cervical intraepithelial neoplasia. The underlying mechanisms of BC at cellular, genetic, and molecular levels remain to be ascertained. Oral BC supplement is well-tolerated, but some people may experience problems such as flatulence and nausea. Well-designed, randomized, placebo-controlled, clinical trials are needed to access the therapeutic potential, long-term safety, and optimal doses of BC products. This review is aimed to highlight the anticancer potential of BC and its components, and the therapeutic applications of BC supplements in treating gastrointestinal diseases in children and adults. We also discuss the health promotion benefits and therapeutic potential of BC nutraceuticals in reducing the incidence of non-communicable diseases., (Copyright © 2020 Bagwe-Parab, Yadav, Kaur, Tuli and Buttar.)

In this article, we report a simple, cost-effective and eco-friendly method of airbrushing for the fabrication of antibacterial composite nanofibers using Nylon-6 and silver chloride (AgCl). The Nylon-6 is a widely used polymer for various biomedical applications because of its excellent biocompatibility and mechanical properties. Similarly, silver has also been known for their antibacterial, antifungal, antiviral, and anti-inflammatory properties. In order to enhance the antibacterial functionality of the Nylon-6, composite nanofibers in combination with AgCl have been fabricated using airbrush method. The chemical functional groups and morphological studies of the airbrushed Nylon-6/AgCl composite nanofibers were carried out by FTIR and SEM, respectively. The antibacterial activity of airbrushed Nylon-6/AgCl composite nanofibers was evaluated using Gram +ve (Staphylococcus aureus) and Gram -ve (Escherichia coli) bacterial strains. The results showed that the airbrushed Nylon-6/AgCl composite nanofibers have better antibacterial activity against the tested bacterial strains than the airbrushed Nylon-6 nanofibers. Therefore, the airbrushed Nylon-6/AgCl composite nanofibers could be used as a potential antibacterial scaffolding system for tissue engineering and regenerative medicine.

A wide variety of chronic diseases, such as neurodegenerative and cardiovascular disorders, diabetes mellitus, osteoarthtitis, obesity and various cancers, are now being treated with cost effective phytomedicines. Since synthetic medicines are very expensive, concerted efforts are being made in developing and poor countries to discover cost effective medicines for the treatment of non-communicable diseases (NCDs). Understanding the underlying mechanisms of bioactive medicines from natural sources would not only open incipient avenues for the scientific community and pharmaceutical industry to discover new drug molecules for the therapy of NCDs, but also help to garner knowledge for alternative therapeutic approaches for the management of chronic diseases. Fisetin is a polyphenolic molecule of flavonoids class, and belongs to the bioactive phytochemicals that have potential to block multiple signaling pathways associated with NCDs such as cell division, angiogenesis, metastasis, oxidative stress, and inflammation. The emerging evidence suggests that fisetin may be useful for the prevention and management of several types of human malignancies. Efforts are being made to enhance the bioavailability of fisetin after oral administration to prevent and/or treat cancer of the liver, breast, ovary and other organs. The intent of this review is to highlight the in vitro and in vivo activities of fisetin and to provide up-to-date information about the molecular interactions of fisetin with its cellular targets involved in cancer initiation, promotion and progression as well as to focus on strategies underway to increase the bioavailability and reduce the risk of deleterious effects, if any, associated with fisetin administration., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Inflammation-induced endothelial abnormalities, dietary habits, and tobacco smoking are considered to be the primary risk factors for causing atherosclerosis and Cardiovascular Diseases (CVDs), including Coronary Heart Disease (CHD), cerebrovascular disorders, peripheral arterial disease, rheumatic heart disease, congenital heart defects, deep vein thrombosis and pulmonary embolism. Prevention of CVDs with anti-inflammatory and anti-oxidant agents has been a challenging task for decades. Currently, CVDs have taken a top position among the health-related issues and are considered the foremost cause of mortality and morbidity around the globe., Objective: Emerging evidence from several sources indicates that nutraceuticals and plant products may be a cost-effective approach for the prevention of CVDs. A limited number of clinical studies done with nutraceuticals have shown positive effects for promoting health and well-being as well as reduction of CVDs in humans. Some plants from which nutraceutical ingredients are isolated and will be discussed in this review are: Murraya koenigii, Curcuma longa, Beta vulgaris, Allium sativum, Allium cepa, Lagenaria siceraria Stand, Trigonella foenum-graecum., Methods: Literature searches were done using keywords for plants, nutraceuticals, and plant products that have revealed beneficial effects in the prevention of CVDs. The anti-oxidant and anti-inflammatory actions of nutraceuticeuticals and plant ingredients play a significant role in capturing free radicals and reducing endothelial risk factors associated with the occurrence CVDs., Results: This review has explored the usefulness of animal studies performed with nutraceuticals and herbal products and to understand their mode of action in the prevention of CVDs. Also, we have referred to patents for different nutraceuticals for better understanding their quantitative effects and dosage forms., Conclusion: It is concluded that nutraceuticals possess enormous health benefits and their interventions can be highly beneficial in the prevention/reduction of CVDs and related disorders such as atherosclerosis, hypertension, heart attack and stroke. The findings of this review provide an update on the emerging uses of nutraceuticals, functional foods, and herbal remedies in humans. Nevertheless, large-scale randomized, placebo-controlled, double-blind clinical trials are needed to confirm the health benefit claims about nutraceuticals and herbal products to establish their long-term safety and to resolve the controversy about the role of clinical nutrition in curing lifestyle diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans. This included food color, flavor, and aroma, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer's disease. Impairment of olfactory and gustatory function in relation to these diseases was also explored. The role of functional foods was considered as a potential treatment of dementia and Alzheimer's disease through inhibition of acetylcholinesterase as well as similar treatments based on herbs, spices and antioxidants therein. The importance of antioxidants for maintaining the physiological functions of liver, kidney, digestive system, and prevention of cardiovascular diseases and cancer has also been highlighted. Detailed discussion was focused on health promotion of the older person through the frequency and patterns of dietary intake, and a human ecology framework to estimate adverse risk factors for health. Finally, the role of the food industry, mass media, and apps were explored for today's new older person generation., Competing Interests: The authors declare no conflicts of interest.

Mediterranean-style diets caused a significant decline in cardiovascular diseases (CVDs) in early landmark studies. The effect of a traditional Mediterranean diet on lipoprotein oxidation showed that there was a significant reduction in oxidative stress in the intervention group (Mediterranean diet + Virgin Olive Oil) compared to the low-fat diet group. Conversely, the increase in oxidative stress causing inflammation is a unifying hypothesis for predisposing people to atherosclerosis, carcinogenesis, and osteoporosis. The impact of antioxidants and anti-inflammatory agents on cancer and cardiovascular disease, and the interventive mechanisms for the inhibition of proliferation, inflammation, invasion, metastasis, and activation of apoptosis were explored. Following the Great Oxygen Event some 2.3 billion years ago, organisms have needed antioxidants to survive. Natural products in food preservatives are preferable to synthetic compounds due to their lower volatility and stability and generally higher antioxidant potential. Free radicals, reactive oxygen species, antioxidants, pro-oxidants and inflammation are described with examples of free radical damage based on the hydroxyl, nitric oxide and superoxide radicals. Flavonoid antioxidants with 2- or 3-phenylchroman structures such as quercetin, kaempferol, myricetin, apigenin, and luteolin, constituents of fruits, vegetables, tea, and wine, which may reduce coronary disease and cancer, are described. The protective effect of flavonoids on the DNA damage caused by hydroxyl radicals through chelation is an important mechanism, though the converse may be possible, e.g., quercetin. The antioxidant properties of carotenoids, which are dietary natural pigments, have been studied in relation to breast cancer risk and an inverse association was found with plasma concentrations: higher levels mean lower risk. The manipulation of primary and secondary human metabolomes derived especially from existing or transformed gut microbiota was explored as a possible alternative to single-agent dietary interventions for cancer and cardiovascular disease. Sustained oxidative stress leading to inflammation and thence to possibly to cancer and cardiovascular disease is described for spices and herbs, using curcumin as an example of an intervention, based on activation of transcription factors which suggest that oxidative stress, chronic inflammation, and cancer are closely linked.

Background: Human milk contains a number of nutrients and bioactive ingredients which play an important role in the growth and development of infants. One important nutrient and bioactive ingredient of human milk is L-tryptophan. L-Tryptophan is an essential aromatic α-amino acid and is required in the diet of children and adult humans. As an essential amino acid, it is needed for protein synthesis and as a precursor of key biomolecules such as serotonin, melatonin, tryptamine, niacin, quinolinic acid and kynurenic acid, nicotinamide adenine dinucleotide. The aim of the study was to evaluate the antioxidant, anti-inflammatory and antiproliferative properties of tryptophan isolated from enzymatic hydrolysates from human milk and its metabolites on human glioma U251 cells and to evaluate the effects of human recombinant (hrIFNγ) on molecular ions of tryptophan and its metabolites in human glial U251 cells., Methods: The cytotoxicity was determined by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. The antioxidant property was assessed by the oxygen radical scavenging capacity (ORAC) method. The anti-inflammatory effect was determined by the enzyme-linked immunosorbent assay (ELISA) against cytokines IL-6 and TNF-α. The effects of recombinant human (rhIFNγ) on molecular ions of tryptophan and its catabolites were evaluated by mass spectrometry. The tryptophan was isolated from milk peptides following enzymatic digestion, followed by separation by chromatographic and mass spectrometric methods., Results: Tryptophan from human milk exhibited profoundly higher oxygen radical absorption capacity (7,986±468 µm Trolox equivalent (TE)/g) than that of whole human milk (80.4±13.3 µm TE/g). Tryptophan showed a moderate degree of anti-inflammatory activity against TNF-α and IL-6. rhIFNγ inhibited tryptophan metabolism. A low concentration of L-tryptophan (10-25 μg/mL) inhibited nearly 25% of cell growth. When U251 cells were treated with 25 μg/mL L-tryptophan and subsequently challenged with 30 ng/mL of human recombinant IFNγ, a significant inhibitory effect on cell growth was observed. Low concentrations of Xanthurenic acid, L-kynurenine, and 3-OH DL kynurenine were found to inhibit cell growth except melatonin and 3-OH anthranilic acid. Melatonin was a strong inducer of TNF-α in RAW cells, whereas 3-OH kynurenine at 25, 50 and 100 µg/mL inhibited IL-6 in RAW cells. No significant change was observed in the IL-8 profile in tryptophan-treated U251 cells except that L-kynurenine at 10 µg/mL produced significantly high level of an inflammatory cytokine IL-8. Melatonin, 3-OH, DL kynurenine at high concentrations (100 µg/mL) induced proliferation of U251 cells. Melatonin seemed to show synergistic effects with recombinant human IFNγ (rhINFγ) in promoting growth of human glioma cells. While treatment of U251 cells with tryptophan alone and subsequent treatment with rhIFNγ inhibited the growth of human cancer glioma cells, and conversely melatonin combined with rhIFNγ promoted growth of the U251 cells., Conclusions: The findings from this study suggest that human milk-derived tryptophan and its metabolites possess strong antioxidant properties. Such effects might play a significant role in regulating the cell proliferation and growth of human cancer cells in a concentration-dependent manner.

The present study investigated the infiltration of mast cells into the kidney tissue and the preventive role of mast cell stabilizers against high fat diet (HFD)-induced renal injury in rats. The animals were fed on HFD (30% fat) for 12 consecutive weeks to induce renal injury. The HFD-induced obesity was assessed by calculating obesity index, adiposity index, and estimation of total cholesterol, triglycerides, and high density lipoproteins in plasma. The renal dysfunction was evaluated by measuring creatinine clearance, blood urea nitrogen, uric acid, electrolytes and microproteinuria. The oxidative stress in renal tissues was determined by myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation and reduced glutathione level. The systolic blood pressure (SBP) was monitored using non-invasive blood pressure measuring apparatus. Histamine and hydroxyproline contents were quantified in renal tissues. Gross histopathological changes, mast cell density and collagen deposition in the renal tissue was determined by means of histopathology. The mast cell stabilizers, sodium cromoglycate and ketotifen were administered daily for 12 weeks. The HFD fed rats demonstrated significant increase in lipid profile, kidney injury with marked increase in renal oxidative stress, SBP, mast cell density, histamine content and hydroxyproline content that was attenuated by sodium cromoglycate and ketotifen treatment. Hence, the novel findings of this investigation suggest that HFD induced mast cells infiltration into kidney tissue seems to play an important role in renal pathology, and treatment with mast cell stabilizers serves as potential therapy in management of HFD induced renal dysfunction in rats., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Dipyridamole (DYP) is an anti-platelet agent with marked vasodilator, anti-oxidant, and anti-inflammatory activity. The present study investigated the role of adenosine receptors in DYP-mediated protection against ischemia reperfusion-induced acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h. The renal damage induced by ischemia reperfusion injury (IRI) was assessed by measuring creatinine clearance, blood urea nitrogen, uric acid, plasma potassium, fractional excretion of sodium, and microproteinuria in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The hematoxylin-eosin staining was carried out to observe histopathological changes in renal tissues. DYP (10 and 30 mg/kg, intraperitoneal, i.p.) was administered 30 min before subjecting the rats to renal IRI. In separate groups, caffeine (50 mg/kg, i.p.), an adenosinergic A1 and A2A receptor antagonist was administered with and without DYP treatment before subjecting the rats to renal IRI. The ischemia reperfusion-induced AKI was demonstrated by significant changes in serum as well as urinary parameters, enhanced oxidative stress, and histopathological changes in renal tissues. The administration of DYP demonstrated protection against AKI. The prior treatment with caffeine abolished DYP-mediated reno-protection suggesting role of A1 and A2A adenosine receptors in DYP-mediated reno-protection in rats. It is concluded that adenosine receptors find their definite involvement in DYP-mediated anti-oxidative and reno-protective effect against ischemia reperfusion-induced AKI.

Background: The present study was designed to examine the anti-inflammatory effects of plant-derived products marketed for human health benefits., Methods: The tumor necrotic factor-α (TNF-α) was used as a proinflammatory biomarker generated by mouse macrophage RAW 264.6 cells. The in vitro tested plant products include Saskatoon berry (SKB), quercetin, purified oat beta-glucan (OBG), curcumin, and turmeric. Quantification of TNF-α in cell culture supernatants was carried out using mouse TNF-α assay kit and the cell proliferation was determined by MTT (3-(4, 5-dimethylthiazolyl-2)-2,5- diphenyltetrazolium bromide) assay. The cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% heat-inactivated fetal bovine serum and 100 U/mL penicillin and 100 µg/mL streptomycin. Bacterial lipopolysaccharide (LPS) at a concentration of 500 ng/mL was employed to stimulate the TNF-α production in mouse macrophage cells., Results: Results showed that curcumin at 10 µM (3.7 µg/mL) level effectively attenuated the LPS-induced inflammatory response, and at 100 µM completely inhibited macrophage RAW cell growth (p<0.05). The aqueous turmeric extract caused inhibitory effect on TNF-α at 25, 50, 100, and 500 µg/mL. SKB inhibited TNF-α production at 50, 100, 500, and 1,000 µg/mL. On the other hand, at 10, 25, 500, and 1,000 µg/mL SKB promoted significant cell growth/proliferation. Quercetin at 10, 25, 50 and 100 µg/mL inhibited TNF-α, but at 500 and 1,000 µg/mL stimulated cell growth. OBG at 10, 25, and 50 µg/mL inhibited TNF-α, but in some cases OBG stimulated TNF-α At 1,000 and 10,000 µg/mL OBG proved to be extremely toxic or lethal to the macrophage cells., Conclusions: Overall, the plant products showed anti-inflammatory effects as well as cell proliferation or inhibition in the in vitro system used in this investigation. The underlying mechanisms of dualistic actions caused by plant-derived ingredients, viz., macrophage cellular growth stimulation or retardation, remain to be elucidated.

Context: Immunity related disorder is one of the leading causes of disease in the world. Oxidative stress and microbial infections play a major role in inflammation-induced diseases. Bovine colostrum (BC) contains immunoglobulins and lactoferrins which help in building the immunity and protect against the bacterial proliferation and growth., Aim: This study was designed to investigate the antimicrobial and antiinflammatory activities of BC., Materials and Methods: Antimicrobial activity was determined by the pour-plate method using five different strains of bacteria (Gram -ve and +ve), and carrageenan-induced rat paw edema method was used for the evaluation of antiinflammatory activity in adult Wistar rats. Diclofenac was used as standard antiinflammatory drug, and amoxicillin was used as standard antimicrobial agent., Results: BC showed significant antimicrobial activity against Escherichia. coli, Staphylococcus. aureus, Proteus. vulgaris, Enterobacter. aerogenes and Salmonella. typhi. At 100 µg/mL of BC, the inhibition zones were found to be 13mm, 11mm, 12mm, 12mm, and 11mm, respectively. The BC zones were comparatively smaller than those of amoxicillin at 10µg/mL, where the inhibition zones were 16mm, 30mm, 23mm, 22mm and 23mm, respectively. In the BC treated animals, the percentage edema inhibition was found to be 67.94% at the third hour, suggesting high antiinflammatory activity of BC in rats., Conclusion: BC may be beneficial in reducing the risks of inflammation associated diseases. Further studies are needed before BC can be recommended for therapeutic interventions in humans.

Background: Fibrous structures and synthetic polymer blends offer potential usages in making biomedical devices, textiles used in medical practices, food packaging, tissue engineering, environmental applications and biomedical arena. These products are also excellent candidates for building scaffolds to grow stem cells for implantation, to make tissue engineering grafts, to make stents to open up blood vessels caused by atherosclerosis or narrowed by blood clots, for drug delivery systems for micro- to nano-medicines, for transdermal patches, and for healing of wounds and burn care. The current study was designed to evaluate the antimicrobial activity of woven and non-woven forms of nano- and macro-scale blended polymers having biocompatible and biodegradable characteristics., Methods: The antimicrobial activity of non-woven fibrous structures created with the combination of synthetic and biopolymer was assessed using Gram-negative, Gram-positive bacteria, such as Staphylococcus aureus, Proteus vulgaris, Escherichia coli and Enterobacter aerogenes using pour plate method. Structural evaluation of the fabricated samples was performed by Fourier transform infrared spectroscopy., Results: Broad spectrum antibacterial activities were found from the tested materials consisting of polyvinyl alcohol (PVA) with chitosan and nylon-6 combined with chitosan and formic acid., Conclusions: The combination of PVA with chitosan was more bactericidal or bacteriostatic than that of nylon-6 combined with chitosan and formic acid. PVA combination with chitosan appears to be a broad-spectrum antimicrobial agent.

Background: The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent., Objective: The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression., Materials and Methods: Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose-finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT)., Results: Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic-serotonergic neurotransmission pathway, which is the hallmark of selective serotonin reuptake inhibitors (SSRI) class of drugs., Conclusion: The results obtained in this study suggest that combined administration of MOE with low doses of fluoxetine or other SSRI drugs seems to have promising potential.

Nutraceutical, a term combining the words "nutrition" and "pharmaceuticals", is a food or food product that provides health benefits as an adjuvant or alternative therapy, including the treatment and prevention of infectious diseases in children and adults. There is emerging evidence that bovine colostrum (BC) may be one of the promising nutraceuticals which can prevent or mitigate various diseases in newborns and adults. Immunity-related disorders are one of the leading causes of mortality in the world. BC is rich in immunity, growth and antimicrobial factors, which promote tissue growth and the maturation of digestive tract and immune function in neonatal animals and humans. The immunoglobulins and lactoferrin present in colostrum are known to build natural immunity in newborns which helps to reduce the mortality rate in this population. Also, the side-effect profile of colostrum proteins and possible lactose intolerance is relatively less in comparison with milk. In general, BC is considered safe and well tolerated. Since colostrum has several important nutritional constituents, well-designed, double-blind, placebo-controlled studies with colostrum products should be conducted to widen its therapeutic use. The objectives of this review are to create awareness about the nutraceutical properties of colostrum and to discuss the various ongoing alternative treatments of colostrum and its active ingredients as well as to address colostrum's future nutraceutical and therapeutic implications in humans.

Curcumin is a highly potent, nontoxic, bioactive agent found in turmeric and has been known for centuries as a household remedy to many ailments. The only disadvantage that it suffers is of low aqueous solubility and poor bioavailability. The aim of the present study was to develop a method for the preparation of nanoparticles of curcumin with a view to improve its aqueous-phase solubility and examine the effect on its antimicrobial properties. Nanoparticles of curcumin (nanocurcumin) were prepared by a process based on a wet-milling technique and were found to have a narrow particle size distribution in the range of 2-40 nm. Unlike curcumin, nanocurcumin was found to be freely dispersible in water in the absence of any surfactants. The chemical structure of nanocurcumin was the same as that of curcumin, and there was no modification during nanoparticle preparation. A minimum inhibitory concentration of nanocurcumin was determined for a variety of bacterial and fungal strains and was compared to that of curcumin. It was found that the aqueous dispersion of nanocurcumin was much more effective than curcumin against Staphylococcus aureus , Bacillus subtilis , Escherichia coli , Pseudomonas aeruginosa , Penicillium notatum , and Aspergillus niger . The results demonstrated that the water solubility and antimicrobial activity of curcumin markedly improved by particle size reduction up to the nano range. For the selected microorganisms, the activity of nanocurcumin was more pronounced against Gram-positive bacteria than Gram-negative bacteria. Furthermore, its antibacterial activity was much better than antifungal activity. The mechanism of antibacterial action of curcumin nanoparticles was investigated by transmission electron micrograph (TEM) analysis, which revealed that these particles entered inside the bacterial cell by completely breaking the cell wall, leading to cell death.

Hypertension, myocardial infarction, atherosclerosis, arrhythmias and valvular heart disease, coagulopathies and stroke, collectively known as cardiovascular diseases (CVDs), contribute greatly to the mortality, morbidity and economic burden of illness in Canada and in other countries. It has been estimated that over four million Canadians have high blood pressure, a comorbid condition that doubles or triples the risk of CVD. According to the Heart and Stroke Foundation of Canada, CVDs caused 36% of deaths in 2001 and were responsible for 18% of the total hospital costs in Canada. The majority of Canadians exhibit at least one CVD-related risk factor, such as tobacco smoking, physical inactivity, diabetes, obesity, hypertension, a lack of daily fruit and vegetable consumption, and psychosocial factors, making these people more prone to developing a serious CVD-related illness in the future. It is therefore important that CVD-related causes and concerns be addressed. Given the scope and prevalence of CVDs, it is obvious that a population health approach - 'prevention is better than cure' - would be the most appropriate model to adopt to deal with this ubiquitous health problem and to reduce the costs of hospitalization, long-term medication and rehabilitation. The focus of the present review is to evaluate and compare the results of epidemiological, experimental and clinical studies, reporting on the influence of physical activity, dietary intervention, obesity and cigarette smoking on cardiovascular health and the prevention of CVDs. The prophylactic measures must be dealt with collectively because there is overwhelming evidence that the occurrence of CVDs can be reduced by approximately 80% by making lifestyle modifications. The preventive strategies against CVDs must be targeted at a primary health promotion level before some of the important underlying causes of CVD seriously afflict a person or a population at large. Such preventive approaches would help in reducing not only employee absenteeism but also the hospital and drug costs burdening the health care systems of both developed and developing countries.

Recently, drug interactions with grapefruit juice (GFJ) have received considerable attention from basic scientists, physicians, industry and drug regulatory agencies. GFJ has been shown to inhibit cytochrome P-450 3A4 isoenzyme and P-glycoprotein transporters in the intestine and liver. The GFJ-induced inhibitory effects are considered to be responsible for alterations in drug bioavailability, and pharmacokinetic and pharmacodynamic changes when drugs are ingested concurrently with GFJ. However, little or no interaction is observed when GFJ is taken concomitantly with parentally administered drugs. It is well known that risk factors for cardiovascular disease increase with advancing age, while hepatic metabolic activity decreases in elderly individuals. It is, therefore, possible that the combination of GFJ and cardiovascular medications may pose a health risk, especially in elderly patients. A number of studies have shown interactions of GFJ with cardiovascular drugs such as calcium-channel blockers, angiotensin II receptor antagonists, beta-blockers, and statins. Such interactions are likely to change the pharmacokinetics and pharmacodynamics of these drugs, consequently causing undesirable health effects. Therefore, health care professionals and the public need to be advised of the potential risks associated with the concomitant use of GFJ and interacting medications, especially cardiovascular drugs and agents with a narrow therapeutic index. This review focuses on the adverse interactions of GFJ and cardiovascular medications, and the proposed underlying mechanisms of such interactions.

The renin-angiotensin system is associated with a variety of pathophysiological processes in many organ systems, and is known to be involved in the normal regulation of blood pressure and in the pathogenesis of renovascular hypertension. Angiotensin II is a multifunctional hormone that manifests its properties by interacting with two major subtypes of cell surface receptors (AT1 and AT2). Angiotensin converting enzyme (ACE) inhibitors are able to modify the actions of the renin-angiotensin system, and are indicated for the treatment of hypertension and heart disease. The antihypertensive effects of ACE inhibiting drugs are related to their ability to block the conversion of the decapeptide, angiotensin I, to the potent pressor octapeptide, angiotensin II. ACE inhibitors have been implicated in fetopathies in humans and perinatal mortality in rats, rabbits, sheep and baboons. Human fetopathies were seen when ACE inhibitors were given around the 26th week of gestation. The major adverse effects in babies include: oligohydramnios, renal tubular dysgenesis, neonatal anuria, calvarial and pulmonary hypoplasia, mild to severe intrauterine growth retardation, persistent patent ductus arteriosus and fetal or neonatal death. These developmental anomalies are thought to be partly due to a direct action of ACE inhibitors on the fetal renin-angiotensin system and partly due to the ischemia resulting from maternal hypotension and decreases in fetal-placental blood flow and oxygen/nutrient delivery to the fetus. The purpose of this review is to briefly discuss the pathophysiological role of the renin-angiotensin system, the therapeutic uses of ACE inhibitors in pregnant patients and to focus primarily on the major fetotoxic effects of ACE inhibitors encountered in humans and animal models. I will also review our recent data which show that capozide (captopril + hydrochlorothiazide) not only produces oligohydramnios but also disturbs the balance of glucose and NaCl in the maternal plasma and amniotic fluid of the rat.

Despite overwhelming and tragic evidence of their detrimental and dangerous consequences, amphetamines remain significant drugs of abuse and addiction. The effects of 4-substituted amphetamines: 4-hydroxyamphetamine (4-HA), 4-methoxyamphetamine (4-MEA), 4-ethoxyamphetamine (4-ETA), 4-propoxyamphetamine (4-PPA), and 4-benzyloxyamphetamine (4-BEA) on intrauterine development, pregnancy outcome, postnatal growth, and survival were compared in Swiss-Webster mice. Single daily doses (0, 50, or 100 mg/kg) of an aqueous solution of different amphetamines were administered on pregnancy days 6 through 18. The 50 mg/kg doses of all amphetamines were well tolerated by the mothers and did not produce any overt signs of maternal toxicity or death. However, a few mothers died on different days of gestation after receiving 100 mg/kg of 4-HA, 4-MEA, 4-ETA, and 4-BEA. The mothers that failed to deliver naturally (3 d after the due date) were killed and their uteri were examined for live/dead fetuses and resorption sites. In comparison with respective controls, the incidence of resorptions was markedly higher in the 4-MEA- and 4-ETA-dosed groups. Delivery was prolonged in the 4-PPA- and 4-BEA-treated dams. Apparently well-formed but dead pups were delivered by 4-HA-, 4-PPA-, and 4-BEA-dosed mice. Marked reductions in average litter size and weight occurred after intrauterine exposure to 100 mg/kg 4-BEA. Treatment with 4-ETA, 4-PPA, and 4-BEA not only resulted in a high incidence of cannibalism within 24 h after birth but also caused an increase in cumulative pup mortality during the first 3 weeks of age. Body weight gain was significantly lower in 3-week-old offspring exposed to 4-HA and 4-PPA than in the controls. The findings suggest that 4-substituted amphetamines exhibit a wide variation in their effects on maternal toxicity and pregnancy wastage, and produce adverse effects on parturition, pup survival, and postnatal development.

(i) The urinary elimination of methoxyphenamine (MPA) and its metabolites in underivatized samples was examined after single and multiple oral administration to pregnant and non-pregnant mice by GLC and GLC-MS. (ii) The major metabolite O-desmethylmethoxyphenamine (ODMP), along with lesser amounts of N-desmethylmethoxyphenamine (NDMP) and 2-hydroxyamphetamine (2OH), were the only metabolites detected in urine extracts of pregnant and non-pregnant mice. 5-Hydroxymethoxyphenamine (5HMP) was not detected. Enzyme hydrolysis did not increase the recovery of either substrate or metabolites in either the pregnant or non-pregnant animals. The results show that MPA metabolism in the Swiss-Webster mouse is distinctly different from that seen in man and other laboratory animals. (iii) The mean MPA:ODMP ratio in day-6 urine from pregnant mice after a single dose was 0.31 +/- 0.04. The NDMP:ODMP ratios were less than 0.10 in all samples. Non-pregnant mice urine had equivalent amounts of MPA, NDMP, ODMP, and 2OH after multiple dosing. (iv) While multiple dosing and pregnancy did not alter either the urinary recovery or profile of the metabolites detected, there was a linear decrease in the MPA:ODMP ratio during gestation. (v) MPA was extensively metabolized to ODMP in the male mice, and the MPA:ODMP ratio of 0.41 was slightly higher than that observed in the pregnant and non-pregnant females.

Ingestion of the anticonvulsant drug valproic acid and of the angiotensin converting enzyme inhibitor captopril during pregnancy has been associated with abnormal fetal outcome in humans. In contrast, the use of the antiinflammatory drug ibuprofen and the antihistamine diphenhydramine has not been documented to be embryotoxic in humans. We evaluated the rat embryo culture system as a predictive model of teratogenesis, using these four drugs as test agents. Valproic acid, ibuprofen, and diphenhydramine were embryotoxic, inducing concentration-dependent decreases in growth and a significant increase in anomalies. Valproic acid caused an increase in neural tube defects, ibuprofen increased the incidence of abnormal maxillary processes, and diphenhydramine increased the number of embryos with distorted body morphology. These abnormalities were induced at concentrations of valproic acid and diphenhydramine that are used clinically, but ibuprofen only induced toxicity at concentrations greatly exceeding the therapeutic range. Captopril was not embryotoxic up to 5 mM, the highest concentration tested. These results suggest that the rat embryo culture system produces both false positive and false negative data on the teratogenic potential of drugs. Although such an in vitro assay may be suitable to determine the mechanism of teratogenesis, it is not a sensitive indicator of potential human teratogens on its own. These data support the view that in vitro systems can only supplement clinical and epidemiological observations in humans, possibly as a method to determine mechanisms of actions of teratogens.

The urinary elimination of 4-hydroxyamphetamine (PHA) and a series of homologous 4-alkoxy-substituted amphetamines and their metabolites was examined after single and multiple oral administration to pregnant and non-pregnant mice. The metabolic profile and extent of biotransformation in a series of alkoxy analogues were affected by the size of the alkoxy side chain, multiple dosing and pregnancy. There were increased recoveries of both the substrate and the conjugated derivative of PHA during gestation. The major metabolic routes observed were O-dealkylation, conjugation, and aliphatic hydroxylation of the propoxy side chain. There was some evidence of oxidative deamination. Pregnancy did not alter the profile of the major metabolites detected by GLC and NMR spectroscopy.

The potential for the antibacterial agent ciprofloxacin to interfere with the disposition of the antiviral agent dideoxyinosine (ddI) was evaluated in adult male Wistar rats. The combination group (n = 10) was dosed orally with 100 mg/kg ciprofloxacin in water every 12 h for three consecutive doses. Thirty minutes after the last dose, a bolus IV injection of 50 mg/kg 14C-ddI in physiologic saline was given over 7-10 sec through the penile vein. The control group (n = 8) received a single dose of IV 14C-ddI. Blood, urine and fecal samples were collected from 0-4 h, and tissue samples were removed at 4 h after ddI administration. The disappearance of 14C from blood followed the kinetics of a two-compartment model with bolus input and first-order output. The following pharmacokinetic parameters (mean +/- SD) were calculated based on total blood radioactivity for the 14C-ddI alone and combination groups, respectively: blood clearance 13.5 +/- 2.0 vs. 12.7 +/- 1.5 ml/min/kg, terminal disposition half-life 49.9 +/- 2.2 vs. 49.0 +/- 6.0 min, steady-state volume of distribution 891 +/- 134 vs. 825 +/- 126 ml/kg, mean residence time 66.2 +/- 3.1 vs. 65.0 +/- 7.8 min (the power to detect a 20% decrease in the above parameters, relative to the reference ddI alone, was > 85% at the 5% significance level), percentage of administered dose recovered in urine 62.2 +/- 9.8% vs. 56.6 +/- 13.0%. Most of the radioactivity in tissues was concentrated in the liver, adrenal, spleen and kidney. Except for significant decreases (p < 0.05) in the levels of 14C in skeletal muscle and cecum of combination treated rats, the coadministration of ciprofloxacin showed no differences in either the tissue levels of 14C or the pharmacokinetic parameters of 14C-ddI-derived radioactivity. The results obtained with total 14C measurements suggest that ciprofloxacin does not alter the disposition of ddI in the rat, although unchanged ddI was not determined.