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Thursday, March 23, 2017

Traditional use of medicinal plants to combat disease: special journal issue


Submission is open for an ethnopharmacology-focused special issue of the journal Frontiers in Pharmacology (IF=4.4, Q1), guest edited by Atanas G. Atanasov, Judith Maria Rollinger, Judit Hohmann, and Anna Karolina Kiss.

With emphases of traditional European medicine, the special issue encourages submissions related to phytochemistry, clinical studies with herbal preparations, bioactivities and mechanism of action studies with natural products, pharmacokinetics and biotransformation of phytochemicals, field and observational studies on the use of local and traditional medicinal plants etc.



The submission of the following article types is particularly encouraged: Original Research, Methods, Protocols, Technology Reports, Reviews, Mini-Reviews, Hypothesis & Theory, Perspectives, Data Reports, General Commentary, Opinions, and Book Reviews.

The full text of the submission call with all further details and requirements can be viewed at:

http://journal.frontiersin.org/researchtopic/6024/ethnopharmacology-in-central-and-eastern-europe-in-the-context-of-global-research-developments



Sunday, March 19, 2017

The novel dietary supplement methylsulfonylmethane (MSM): applications and safety


Abstract (as presented by the authors of the scientific work):

"Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusions (as presented by the authors of the scientific work):

"MSM is a naturally occurring organosulfur compound with broad biological effects. Human absorption and biosynthesis of this compound likely depends heavily on the co-metabolism between microbiota and host. Whether naturally produced or manufactured, MSM exhibits no biochemical differences in its ability to intermediate oxidative stress and inflammation. This micronutrient is well tolerated for arthritis and a number of other conditions related to inflammation, physical function, and performance. Emerging research suggests that MSM may one day aid in the treatment of various types of cancer [49,99,100,101,119,120,121,122,123,125,126,181,184,185,186,194] or metabolic syndromes [195]."


Full-text access of the referenced scientific work:

Butawan M, Benjamin RL, Bloomer RJ. Methylsulfonylmethane: Applications and
Safety of a Novel Dietary Supplement. Nutrients. 2017 Mar 16;9(3). pii: E290.
doi: 10.3390/nu9030290. Review. PubMed PMID: 28300758.
http://www.mdpi.com/2072-6643/9/3/290/htm


Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At


Thursday, March 16, 2017

Stress-induced despair behavior and intestinal microbiota: can eating yogurt combat depression?


Abstract (as presented by the authors of the scientific work):

"Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Discussion (as presented by the authors of the scientific work):

"Taken together, our results demonstrate that microbiome homeostasis was robustly altered in animals undergoing UCMS, with a consistent decrease in Lactobacilli. This finding was shared across three strains of mice (C57BL/6J, as BALB/cJ and C57BL/6N). Moreover, our data suggest that the production of H2O2 by Lactobacillus may be protective against the development of despair behavior by direct inhibition of intestinal ido1 expression and decrease in the circulating level of kynurenine, a metabolite associated with depression26.

Our results are in agreement with recent literature demonstrating that microbiome composition is modified with acute and chronic stress20,33,34. Microbiome dysbiosis is also detected in humans affected by major depressive disorders and the transplantation of the biota from these patients in germ free mice can induce despair behavior9. Beyond describing microbiome fluctuation as a consequence of UCMS, we further demonstrated that levels of Lactobacillus correlate with the susceptibility to and severity of despair behaviors. Indeed, animals exhibiting low (i.e. Taconic C57BL/6N mice) intestinal Lactobacillus levels present with a basal despair phenotype, when compared to animals with higher levels of Lactobacillus (i.e. Jackson C57BL/6J mice). Accordingly, therapeutic administration of a probiotic Lactobacillus species during UCMS was sufficient to improve the despair symptoms. Further works will be needed to explore the role of other populations of bacteria affected by UCMS, as well as Lactobacillus strain differences and their abilities to improve behavior.

Recently, members of the Lactobacillus genus have been shown to affect a multitude of aspects of human physiology, as they colonize several sites of the body, including the skin, the vagina, and the entirety of the gastrointestinal tract, starting with the oral cavity35. Perhaps best studied in the vagina, Lactobacilli protect against infection by producing a diversity of antimicrobial factors, including lactic acid, peroxide, bacteriocins, as well as by resource competition35,36,37. Although in a few contexts increased levels of Lactobacilli are associated with pathology, e.g. dental cavities38, the bacteria are largely non-pathogenic or beneficial. From dysbioses or probiotic studies, Lactobacilli are associated with protection against infection, improved recovery after enteric infections, decreased colitis pathology, and better cognitive function25,39,40,41.

While Lactobacilli are able to control other microbial communities through secretion of antimicrobial factors, genetic limitations make them more sensitive to environmental conditions. In particular, many Lactobacillus genus members are unable to synthesize amino acids and purines and thus rely on nutrient rich environments and other bacteria for supply of essential building blocks42,43,44,45. We hypothesize that, in the context of a faster intestinal transit, such as the one observed in stressed animals, fluctuating availability of nutrients and symbiotic bacteria will impact the renewal of the Lactobacillus niche46. Further studies will be able to determine whether there is indeed a causal relationship between increased intestinal motility and microbiota alteration in the context of stress, or rather if the dysbiosis induced during stress causes altered intestinal physiology.

We found that the level of kynurenine is increased after chronic stress, in a manner dependent on Lactobacillus levels. Kynurenine can readily cross the blood-brain barrier to drive depression within the CNS by disrupting neurotransmitter balance and driving neuroinflammation27,47. A recent study by Agudelo et al.26 identified this pathway as also being disrupted in stressed mice using the same model of UCMS. Taken together, these new findings point to disruptions in tryptophan-kynurenine metabolism as an important factor in mediating despair behavior. IDO1 is the main enzyme responsible for conversion of tryptophan to kynurenine outside of the liver, and its expression and activity can be directly inhibited by reactive oxygen species (ROS)32. Members of the Lactobacillus family have the capacity to produce high levels of ROS, as a means of maintaining their niche36,37. In our study, we have shown that decreased levels of ROS in stressed animals correlate with an increase in intestinal ido1 transcripts, thus potentially explaining our observed increase in circulating kynurenine. Moreover, several studies have shown that inhibiting IDO1 activity (such as with the small molecule 1-methyl tryptophan) has potent effects in ameliorating depressive-like behaviors both in chronic stress and inflammation-induced sickness behavior models48,49,50.

The inhibition of IDO1 by Lactobacillus-derived ROS is likely just one of the mechanisms through which Lactobacilli, and L. reuteri in particular, contribute to host physiology and modulate behavior. Our findings are in accordance with the previously reported beneficial effect of L. reuteri administration on despair and anxiety-like behaviors25. Nevertheless, in their study, Bravo and colleagues have shown that L. reuteri can modulate GABA receptor expression in the CNS, via the vagus nerve25. The vagus nerve has been shown to carry peripheral signals and modulate inflammatory and stress reponses51,52,53,54. Whether the two results are connected remains to be investigated. It is possible that intestinal kynurenine can signal on the afferent vagal terminals and modulate its effects in the CNS, including its modulation of the hypothalamus-pituitary adrenal (HPA) axis. To this point, it is important to consider the contribution of liver TDO to peripheral kynurenine levels. TDO expression and activity are increased by glucocorticoids and in response to acute stress, and play a role in glucocorticoid levels homeostasis55,56,57. Whether TDO levels decrease chronically in our long-term stress model (following an expected decrease of corticosterone) or what effect the Lactobacillus administration has remains to be investigated. We have also considered other possible mechanisms for the behavioral effects of L. reuteri supplementation, mediated by the immune system, or other populations of commensals affected by the treatment. Further studies will be necessary to assess the chronological and the hierarchical role of each pathway during despair behavior development, as well as how these pathways affect the CNS.

Altogether, our results indicate that the microbiome can play a causative role in the development and symptomatology of depression. Further studies are needed to prove a causal relationship between intestinal Lactobacillus levels and depressive-like behavior. Moreover, investigation of whether Lactobacilli can play a similar function in human biology and if manipulation of Lactobacillus levels and/or local induction of ROS production in the gut could be used to treat psychiatric disorders is warranted."


Full-text access of the referenced scientific work:
Marin IA, Goertz JE, Ren T, Rich SS, Onengut-Gumuscu S, Farber E, Wu M,
Overall CC, Kipnis J, Gaultier A. Microbiota alteration is associated with the
development of stress-induced despair behavior. Sci Rep. 2017 Mar 7;7:43859. doi:
10.1038/srep43859. PubMed PMID: 28266612; PubMed Central PMCID: PMC5339726.
https://www.researchgate.net/publication/314302451_Microbiota_alteration_is_associated_with_the_development_of_stress-induced_despair_behavior


Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At


Monday, March 13, 2017

The stomach in health and disease


Abstract (as presented by the authors of the scientific work):

"The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):






Conclusions (as presented by the authors of the scientific work):

"Healthy stomach: future approach to gastric diseases

The stomach occupies the central role in orchestrating the digestive process, and this is frequently underestimated. Moreover, gastric acid secretion in the last decades has been seen as a ‘bystander’ with little function but with deleterious potential for itself and adjacent organs, the oesophagus and duodenum. As a consequence, the pharmacological approach has been towards the development of more potent drugs for acid inhibition. Due to the increasing awareness of GI functional disorders, the role of the stomach has been revisited in its role as site of origin for dyspeptic symptoms. More recently, attention has focused on the stomach for its control function in food intake and for contributing to maintenance of metabolic balance (figure 10).

The future approach to gastric diseases (box 3) is directed to maintaining a healthy stomach, which is free from discomfort, ulceration and the risk of complications and malignancy. The main challenge remains the elimination of H. pylori infection from individual patients and from populations. An estimated 20% of H. pylori-infected people will continue to suffer from overt clinical upper GI symptoms and complications over their lifetime, and some may develop extra-digestive diseases. The individual outcome of anyone infected with H. pylori cannot be predicted. Therefore, a public health approach should be directed towards ‘screen and treat’ strategies that will have to be adapted to the needs of different populations according to the prevalence of H. pylori infection and gastric cancer risk stratification. Gastric disease prevention programmes should be integrated with more comprehensive GI prevention strategies. The combination of H. pylori screening and eradication programmes with colorectal cancer screening is an initiative promoted and coordinated by the Healthy Stomach Initiative (HSI) (http://www.hsinitiative.org).

Gastric cancer is still a major challenge worldwide, and because detection is frequently made only at an advanced stage, mortality has remained high.216 ,217 Gastric cancer prevention programmes by H. pylori eradication have been shown of benefit in high-risk populations.193 The best results from gastric cancer prevention strategies are obtained when H. pylori eradication is performed before advanced atrophic gastritis with pre-neoplastic changes becomes established and thus implementation of H. pylori screening and treatment in early adulthood is required. Secondary prevention by H. pylori eradication following endoscopic resection of early gastric cancer has major limitations.218 With pre-neoplastic conditions such as atrophy and IM already present, carcinogenic pathways are more likely to progress in spite of the eradication of H. pylori infection. Future research will need to focus on unravelling mechanisms involved in progression from pre-neoplastic lesions to cancer.

The recent definition of H. pylori gastritis as an infectious disease by the Kyoto global consensus conference, January 2014, is expected to raise concern and engender support from regulatory authorities towards the global elimination of H. pylori infection and its serious sequelae.150

Despite these important indications and calls for a widespread approach to the eradication of H. pylori infection, there remain substantial challenges. The first includes achieving the ideal effective therapy without significant side effects and no antibiotic resistance. Such an ideal therapy is not yet available, and therefore, H. pylori eradication therapy, beyond the established specific clinical indications, should embark on selected screen and treat strategies. For the time being, these strategies will have to address populations with a high to moderate incidence of gastric cancer. The search for a ‘golden treatment bullet’ continues to remain one option while the second option is an intensified search for a vaccine.

Second, H. pylori infection may confer some benefits to those who do not have gastroduodenal symptoms, nor present with gastroduodenal disease or complications. The reduced prevalence of atopic diseases, such as asthma in patients infected with H. pylori up to young adulthood, requires intensive investigation to understand the mechanism of this phenomenon. Epidemiological and experimental evidence is still limited and cannot yet offer any conclusions about a causal relationship.93 ,219 ,220 Studies on the relationship of H. pylori gastritis will lead to better understanding of both local and systemic immune responses and their impact on gastric diseases.

In addition to the initiatives and strategies to eradicate H. pylori infection, studies are required to better understand the role of the stomach in food intake, accommodation, pre-digestion and the delivery of nutrient for intestinal digestion.38 Research should focus on ways to modulate gastric functions and their role as ‘weight watcher’ and their integration in the balance of hunger and satiety. Studies will need to address to what extent gastric acid should be inhibited and for how long during the 24 h period in patients who suffer from acid-related diseases. Moreover, it will be important to define just how much acid is required to preserve a ‘healthy’ gut microbiome. The role of the gastric microbiota in the presence and absence of H. pylori infection on the diversity of microbiota in the small bowel will be of enormous relevance in understanding and tackling gastric, hepatic and intestinal diseases.221–223

Last, but by no means least, education with effective presentation of new knowledge to the general public to ensure gastric health and prevent disease is a major task to be accomplished and the creation of the HSI for public awareness is a step in this direction."


Full-text access of the referenced scientific work:

Hunt RH, Camilleri M, Crowe SE, El-Omar EM, Fox JG, Kuipers EJ, Malfertheiner P, McColl KE, Pritchard DM, Rugge M, Sonnenberg A, Sugano K, Tack J. The stomach in health and disease. Gut. 2015 Oct;64(10):1650-68. doi:10.1136/gutjnl-2014-307595. Review. PubMed PMID: 26342014; PubMed Central PMCID: PMC4835810.
https://www.researchgate.net/publication/281510130_The_stomach_in_health_and_disease


Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At



Sunday, March 12, 2017

How beneficial is Silymarin/Silybin use in chronic liver disease?


Abstract (as presented by the authors of the scientific work):

"
Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusions (as presented by the authors of the scientific work):

"
The “marriage of many years” that links silymarin/silybin to liver diseases, derives from the progressive evidence that, with the passing of time, has led to investigation of, firstly empirically and then scientifically, the mechanisms through which they act in carrying out the therapeutic effect. The studies of pharmacokinetics and pharmacodynamics on silymarin have improved, in the last few years, its applicability in different pathologies, especially liver diseases, allowing, through the use of conjugates compounds, a more efficient application. Through the analysis of literature, it has been demonstrated that silymarin has an effect that allows its use in all of the most frequent causes of liver damage. Indeed, silymarin has three important activities: anti-inflammatory, antioxidant and pro-apoptotic, which represent the “functional triad” that allows for antagonizing the onset and the progression of mechanisms of damage that are responsible for the progression of hepatitis to cirrhosis and HCC. However, it is clear that, also in the end stages of liver pathologies, silymarin can act by limiting de-novo fibrogenesis and antagonizing procarcinogenic mechanisms that cause HCC. Nevertheless, the treatment with silymarin/silybin in routine clinical practice is strongly limited, since it is necessary to obtain scientific data deriving from well-structured trials based on large populations of patients, and to achieve a standardization of methods used for evaluating the therapeutic efficacy, especially in an NAFLD context, that is particularly promising."


Full-text access of the referenced scientific work:

Federico A, Dallio M, Loguercio C. Silymarin/Silybin and Chronic Liver
Disease: A Marriage of Many Years. Molecules. 2017 Jan 24;22(2). pii: E191. doi: 
10.3390/molecules22020191. Review. PubMed PMID: 28125040.
http://www.mdpi.com/1420-3049/22/2/191


Webmaster:


Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At



Thursday, March 9, 2017

Role of intestinal microbiota and metabolites in human diseases


Abstract (as presented by the authors of the scientific work):

"
BACKGROUND:
A vast diversity of microbes colonizes in the human gastrointestinal tract, referred to intestinal microbiota. Microbiota and products thereof are indispensable for shaping the development and function of host innate immune system, thereby exerting multifaceted impacts in gut health.
METHODS:
This paper reviews the effects on immunity of gut microbe-derived nucleic acids, and gut microbial metabolites, as well as the involvement of commensals in the gut homeostasis. We focus on the recent findings with an intention to illuminate the mechanisms by which the microbiota and products thereof are interacting with host immunity, as well as to scrutinize imbalanced gut microbiota (dysbiosis) which lead to autoimmune disorders including inflammatory bowel disease (IBD), Type 1 diabetes (T1D) and systemic immune syndromes such as rheumatoid arthritis (RA).
RESULTS:
In addition to their well-recognized benefits in the gut such as occupation of ecological niches and competition with pathogens, commensal bacteria have been shown to strengthen the gut barrier and to exert immunomodulatory actions within the gut and beyond. It has been realized that impaired intestinal microbiota not only contribute to gut diseases but also are inextricably linked to metabolic disorders and even brain dysfunction.
CONCLUSIONS:
A better understanding of the mutual interactions of the microbiota and host immune system, would shed light on our endeavors of disease prevention and broaden the path to our discovery of immune intervention targets for disease treatment."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusions (as presented by the authors of the scientific work):

"
Intestinal microbiota is normally indispensable for shaping host gut immune system and thus contributing to gut homeostasis maintenance, and is also a key mediator in keeping metabolic functions in the peripheral tissues including liver and pancreas. Accumulating evidence has indicated that intestinal microbiota not only induces and reinforces pro-inflammatory immune responses but also elicits immunosuppressive responses. Abnormal microbial-elicited immunosuppression may result in dysregulation in host metabolism and/or impairment in anti-cancer immunity.

Data with regard to commensal bacteria have integrated, which leads up to a conclusion that a number of microbes are fluctuating on the boundary of virulence. B. fragilis is a representative of this phenomenon. This bacterium is able to improve the development of the host adaptive immune system while being confined to the lumen of the intestinal tract, but becomes enterotoxigenic while it contingently traverses the gut epithelial mucosa. Mazmanian et al [103] showed that during colonization of B. fragilis in animals, a bacterial polysaccharide A (PSA) was presented by DCs, which could direct and promote the maturation of the developing immune system [103]. Subsequent work by the same group substantiated the above finding and further explored the mechanisms of its immunomodulatory effects [129]. Not belonging to dominant members of the gut microbiota, B. fragilis is normally absent in conventionally raised SPF mice. Inoculation with B. fragilis has been found to protect mice from colitis in the T-cell-transferred and TNBS-treated animal models. It appeared that the purified B. fragilis PSA was sufficient to act on host analogous to the live bacterium, including the initiation of IL-10 production by Tregs, suppression of Th17 cell production, disease protection from colitis, and colonization of the host [129, 200]. On the other hand, B. fragilis is capable of producing Bft (Bacteriodes fragilis toxin), which acts indirectly by eliciting high levels of ROS and the ensuing damage of host DNA [201]. Sustained high-leveled ROS, once exceeding the host’s DNA repair capacity, may lead to DNA damage and thereby culminating in cell death or oncogenic mutations [202]. Thus B. fragilis is considered to be a risky factor for colorectal cancer in mammals. Such example also illustrates that a subtle balance is maintained between mammal hosts and microbial kingdom [203].

Mucosal surface barriers are essential for host-microbial symbiosis, the former of which are vulnerable to persistent microbial insults and dietary antigenic components, and must be repaired to re-establish homeostasis. Compromised flexibility of the host or microbiota may place itself on a “death tunnel” to malignancy [202]. In addition, manifestations that immunotherapies are displaying efficacy in malignancies of organs such as melanoma, bladder, renal and lung cancers rather than cancer of the colon, the latter being highly-populated by microbes, have garnered extensive attention as to whether and how the microbiota influences immunotherapy’s efficacy [202]. So the interplays of microbiota and immunotherapy efficacy/toxicity need further investigation.

Among the metabolic disorders, NAFLD, which is characteristic of hepatic triglyceride (TG) accumulation rather than being arisen from alcohol abuse, is linked up with ectopic fat accumulation, especially in the liver. T2D is characterized by persistent hyperglycemia. Pathophysiologic mechanisms of NAFLD and T2D in common are believed to be relevant to insulin resistance, lipotoxicity, and inflammation [171]. Insulin resistance is a multi-organ manifestation as observed at the level of the liver, muscle and adipose tissues. Moreover, adipose tissues and the liver can secrete proinflammatory cytokines. In addition to insulin resistance and inflammation, other risk factors may contribute to the elevated incidence of metabolic diseases including lifestyle (high-fat/sugar diets and poor physical activity), gut microbiota alterations and environmental pollutants.

Based on data heretofore, it is hypothesized that the gut microbiota may mediate the influence of lifestyle factors triggering development of NAFLD and T2D [171]. A metagenome-wide association study on 345 Chinese patients with T2D versus healthy individuals has revealed that T2D sufferers exhibited a moderate degree of gut microbial dysbiosis, referring to a dearth of some butyrate-producing bacteria and an elevation in some opportunistic pathogens [204]. As afore-described in Section of “Liver diseases”, an increased prevalence of Firmicutes, a representation of dysbiosis, is found to be linked to NAFLD [168, 169, 205]. Of particular interest, these two metabolic disorders, NAFLD and T2D, to some extent, share similar mechanisms of etiology: being associated with dysbiosis. These novel findings would broaden our knowledge about metabolic influences of a shifted intestinal microbiota beyond the gut and thus benefit our exploration of therapeutic targets for metabolic diseases.

Close to the completion of this manuscript, an interesting paper has been published demonstrating the link of atherosclerosis etiology with abnormal gut microbiota [206]. Studies with low-density lipoprotein receptor (LDLR) −/− mice, an atherosclerotic murine model, revealed that 12-week supplementation of high-fat diet could lead to evident aortic lesions, macrophage infiltration, and collagen level increase, concurrent with an up-regulation of inflammatory factors [206]. This finding suggests that gut microbiota, combined with metabolisms of fatty acids and vitamin B3, could play a profound role in the onset and development of atherosclerosis [206] (Fig. 3).

A growing body of novel “omics” technologies based on next-generation sequencing, nuclear magnetic resonance (NMR) spectroscopy and gas chromatography coupled with flame ionization detector/mass spectrometry (GC–FID/MS) is gaining wide popularity in the field of cardiometabolic diseases in association with microbiota dysbiosis. The integration and comparison of omics-mode data and molecular biological data would offer comprehensive insight into the mechanisms by which microbiota and metabolites thereof influence host immunity and metabolism. Commensal microbiota in the intestine may serve as a consortium with immunologic and endocrine-like activities to modulate the epigenetic status of host cells. Owing to the advances in genome-wide epigenetic analysis, for instance, chromatin immunoprecipitation sequencing (CHIP-Seq), researchers can determine and analyze these epigenetic modifications, thereby deciphering the intrinsic intestinal microbiota–host interactions and unraveling the impacts of microbiota within and beyond the gut such as liver, cardiovascular system, and even CNS."


Full-text access of the referenced scientific work:

Lin L, Zhang J. Role of intestinal microbiota and metabolites on gut
homeostasis and human diseases. BMC Immunol. 2017 Jan 6;18(1):2. doi:
10.1186/s12865-016-0187-3. Review. PubMed PMID: 28061847; PubMed Central PMCID:
PMC5219689.
https://www.researchgate.net/publication/312145121_Role_of_intestinal_microbiota_and_metabolites_on_gut_homeostasis_and_human_diseases


Webmaster:


Prof. Atanas G. Atanasov (Dr. habil., PhD)
https://about.me/Atanas_At



Tuesday, March 7, 2017

Potential benefits and harms of fasting


Abstract (as presented by the authors of the scientific work):

"Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month) studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):




Conclusions (as presented by the authors of the scientific work):

"This review highlights a lack of high quality data to inform adherence and benefits or harms of IER vs. CER. Research findings and gaps in the evidence comparing IER to CER for weight control and metabolic health are summarised in Table 3. The few randomised comparisons of IER vs. CER amongst overweight and obese subjects report equivalent weight loss, with one trial of a two day low carbohydrate IER reporting greater reductions in body fat compared to CER [13]. These studies were not powered to detect a difference in loss of weight or fat, thus study finding are suggestive but not conclusive of no difference between IER and CER. No studies to date have tested whether IER can prevent weight gain amongst normal weight subjects, however IER regimens based on alternate days of total fasting or marked energy restriction (70% restriction) have not been well tolerated amongst normal and overweight populations (BMI 20–30 kg/m2 ) [15,40]. This review highlights numerous gaps in knowledge of the effects of IER vs. CER on ectopic and visceral fat stores, adipocyte size, FFM, insulin resistance, REE and metabolic flexibility, particularly amongst normal weight subjects. In the absence of these data, we have drawn on findings of short term studies and highlighted some potential beneficial or adverse effects. The variable and sometimes adverse effects of IER on fat stores and metabolism in some rodent models reported in this review are a concern. However, this may relate in part to shifts in night and day eating patterns and circadian rhythm [55], which may not translate to the human situation. Future IER research requires two types of randomised comparison trials. Firstly, longer term RCTs of IER and CER (>6 months) to show whether IER is sustainable long term and has long term benefits or yet undiscovered harmful effects on weight, body composition, and metabolic health compared to CER. Secondly, detailed metabolic proof of principle studies in controlled conditions to assess the effects of IER and matched isoenergetic CER on FFM, hepatic and intramuscular fat stores, insulin sensitivity and metabolic flexibility using robust methodology such as DXA, MRI and insulin clamps. These studies need to assess the metabolic effects of IER during restricted and feed phases of the diet to fully characterise its biological effects amongst people of any weight. Well documented differences in metabolic responses to periods of fasting and marked energy restriction between pre-menopausal women (i.e., increased ketones and free fatty acids) compared to men and post-menopausal women suggest possible different metabolic responses, and perhaps better tolerance to IER within certain populations [85]. Future IER studies should include males, older subjects, individuals with morbid obesity or type 2 diabetes, as well as normal weight subjects. There is also a need to explore optimum patterns of restriction, e.g., two days per week, alternate days, five days per month [86] or other permutations and the best mode of restriction on the restricted and intervening days (e.g., low carbohydrate, low protein). The popularity of IER within the general public coupled with the gaps in the evidence we have identified indicate that IER deserves further rigorous study. We do not know conclusively whether long term IER is a safe effective method of weight control for subjects who are overweight or obese or whether IER may confer health benefits to people of any weight independent of weight loss. High quality research comparing long term outcomes of IER and CER are required to ascertain any true benefits or detrimental effects which IER may have for controlling weight and improving metabolic health in the population."


Full-text access of the referenced scientific work:

Harvie M, Howell A. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects-A Narrative Review of Human and Animal Evidence. Behav Sci (Basel). 2017 Jan 19;7(1). pii: E4. doi: 10.3390/bs7010004. Review. PubMed PMID: 28106818.
http://www.mdpi.com/2076-328X/7/1/4


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Monday, March 6, 2017

Functional components and medicinal properties of food: a scientific review



Abstract (as presented by the authors of the scientific work):

"Research has proved a relationship between functional components of food, health and well-being. Thus, functional components of food can be effectively applied in the treatment and prevention of diseases. They act simultaneously at different or identical target sites with the potential to impart physiological benefits and promotion of wellbeing including reducing the risk of cancer, cardiovascular disease, osteoporosis, inflammation, type II diabetes, and other chronic degenerative diseases, lowering of blood cholesterol, neutralization of reactive oxygen species and charged radicals, anticarcinogenic effect, low-glycaemic response, etc. Previously, it was thought that functional ingredients such as non-starchy carbohydrates including soluble and insoluble dietary fibres, fucoidan; antioxidants including polyphenols, carotenoids, tocopherols, tocotrienols, phytosterols, isoflavones, organosulphur compounds; plant sterols and soy phytoestrogens occur only in plant foods (whole grains, fruits, and vegetables) as phytochemicals. However, probiotics, prebiotics, conjugated linolenic acid, long-chain omega-3, -6 and -9-polyunsaturated fatty acids, and bioactive peptides have proved that functional components are equally available in animal products such as milk, fermented milk products and cold-water fish. The way a food is processed affects its functional components. Many processing techniques have been found to lower the concentration of functional components in food. Conversely, other techniques were found to increase them. Hence, in a time when the role of a healthy diet in preventing non-communicable diseases is well accepted, the borderline between food and medicine is becoming very thin."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusion (as presented by the authors of the scientific work):

"Clearly, functional components in food will play an important role in health maintenance in the future as a result of their medicinal properties. However, the bioavailability of these functional food components and the levels required in humans are critical factors necessary to optimize health benefits. Current information in this regard is insufficient and hazy. Consequently, there is need to provide consumers with more information to effectively guide them in making wider choices of diets that contain optimal levels of health-promoting functional food components."


Full-text access of the referenced scientific work:

Abuajah CI, Ogbonna AC, Osuji CM. Functional components and medicinal properties of food: a review. J Food Sci Technol. 2015 May;52(5):2522-9. doi: 10.1007/s13197-014-1396-5. Review. PubMed PMID: 25892752; PubMed Central PMCID: PMC4397330.


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Sunday, March 5, 2017

The health-promoting potential of Dendrobium species (Orchidaceae)



Abstract (as presented by the authors of the scientific work):

"Dendrobium species, commonly known as "Shihu" or "Huangcao," represents the second largest genus of Orchidaceae, which are used commonly as tonic herbs and healthy food in many Asian countries. The aim of this paper is to review the history, chemistry, and pharmacology of different Dendrobium species on the basis of the latest academic literatures found in Google Scholar, PubMed, Sciencedirect, Scopus, and SID."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusion (as presented by the authors of the scientific work):

"In this paper, the history, chemistry, and pharmacology of different Dendrobium species are reviewed. Especially for biological pharmacology (Table 7). The pharmacological activities examined include antioxidant, anti-inflammatory, immunomodulatory, antitumor, antimicrobial/antifungal, antimutagenic activities, and antiplatelet aggregation activities. The ABTS, DPPH, and hydroxyl radical scavenging effects of different polysaccharides such as DNP, DNP2-1, DNP1-1, DNP3-1, and DNP4-2 have been investigated. Loddigesiinol, nobilone, dihydrophenanthrenes, and phenanthrenes have been evaluated for nitric oxide (NO) scavenging effect. Five types of polysaccharides from D. huoshanense, D. chrysotoxum, and D. fimbriatum species were compared. D. huoshanense and D. chrysotoxum polysaccharides exhibited stronger DPPH and hydroxyl scavenging activity while D. fimbriatum polysaccharides have stronger ABTS scavenging activity. Dihydrophenanthrenes and loddigesiinol D were isolated from D. loddigesii and D. nobile species. Dihydrophenanthrenes significantly inhibited DPPH production. Loddigesiinol D significantly inhibited NO production."


Full-text access of the referenced scientific work:

Lam Y, Ng TB, Yao RM, Shi J, Xu K, Sze SC, Zhang KY. Evaluation of chemical constituents and important mechanism of pharmacological biology in dendrobium plants. Evid Based Complement Alternat Med. 2015;2015:841752. doi: 10.1155/2015/841752. Review. PubMed PMID: 25945114; PubMed Central PMCID: PMC4402476.


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Prof. Atanas G. Atanasov (Dr. habil., PhD)
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Saturday, March 4, 2017

Mushrooms for improvement of health and life quality


 
Abstract (as presented by the authors of the scientific work):

"Mushrooms have been consumed since earliest history; ancient Greeks believed that mushrooms provided strength for warriors in battle, and the Romans perceived them as the "Food of the Gods." For centuries, the Chinese culture has treasured mushrooms as a health food, an "elixir of life." They have been part of the human culture for thousands of years and have considerable interest in the most important civilizations in history because of their sensory characteristics; they have been recognized for their attractive culinary attributes. Nowadays, mushrooms are popular valuable foods because they are low in calories, carbohydrates, fat, and sodium: also, they are cholesterol-free. Besides, mushrooms provide important nutrients, including selenium, potassium, riboflavin, niacin, vitamin D, proteins, and fiber. All together with a long history as food source, mushrooms are important for their healing capacities and properties in traditional medicine. It has reported beneficial effects for health and treatment of some diseases. Many nutraceutical properties are described in mushrooms, such as prevention or treatment of Parkinson, Alzheimer, hypertension, and high risk of stroke. They are also utilized to reduce the likelihood of cancer invasion and metastasis due to antitumoral attributes. Mushrooms act as antibacterial, immune system enhancer and cholesterol lowering agents; additionally, they are important sources of bioactive compounds. As a result of these properties, some mushroom extracts are used to promote human health and are found as dietary supplements."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):




Conclusions (as presented by the authors of the scientific work):

"Several mushroom species have been pointed out as sources of bioactive compounds, in addition to their important nutritional value. The inclusion of whole mushrooms into the diet may have efficacy as potential dietary supplements.

The production of mushrooms and the extraction of bioactive metabolites is a key feature for the development of efficient biotechnological methods to obtain these metabolites. It has been shown by a wide range of studies that mushrooms contain components with outstanding properties to prevent or treat different type of diseases.

Powder formulations of some species have revealed the presence of essential nutrients. They present a low fat content and can be used in low-calorie diets, just like the mushrooms fruiting bodies. Some formulations could be used as antioxidants to prevent oxidative stress and thus ageing.

Future studies into the mechanisms of action of mushroom extracts will help us to further delineate the interesting roles and properties of various mushroom phytochemicals in the prevention and treatment of some degenerative diseases.

In view of the current situation, the research of bioactive components in edible wild and cultivated mushrooms is yet deficient. There are numerous potential characteristics and old and novel properties, provided by mushrooms with nutraceutical and health benefits, which deserve further investigations."


The referenced scientific work at PubMed:

Valverde ME, Hernández-Pérez T, Paredes-López O. Edible mushrooms: improving human health and promoting quality life. Int J Microbiol. 2015;2015:376387. doi: 10.1155/2015/376387. Review. PubMed PMID: 25685150; PubMed Central PMCID: PMC4320875.


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Thursday, March 2, 2017

What is inside the smoke of hallucinogen Salvia divinorum?



Abstract (as presented by the authors of the scientific work):

"Salvia divinorum is a hallucinogen sold over the internet in several forms. Perhaps the most common method of use is smoking the dried leaf material. The sole presumed active constituent, salvinorin A, is a selective kappa-opioid receptor agonist. Upon smoking of the dried leaf material, some of the salvinorin A is destroyed or converted to other materials, leaving in question the actual amount of salvinorin A delivered that leads to the psychotomimetic effect. On average, 133 μg of salvinorin A was delivered in the smoke from an 830 mg per cigarette, which contained ∼2.7 mg of salvinorin A. Hence, only ∼5% of the salvinorin A available in the dried plant material was delivered in the smoke. Upon smoking, hydrolysis of salvinorin A to salvinorin B, an inactive and minor component of the leaf material, also occurs as evidenced by a higher delivered amount of salvinorin B vs salvinorin A (217 vs 133 μg per cigarette). Since smoking is an effective means of achieving the hallucinogenic effect and salvinorin A is the presumed sole active ingredient in the plant, the estimated effective dose of salvinorin A by inhalation is <133 μg per person. Considering the reported rapid metabolism of salvinorin A in vivo, the dose reaching the brain would be substantially less."



Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Results and discussion (as presented by the authors of the scientific work):

"The average values of chemical analytes found in the smoke of a tobacco and an S. divinorum cigarette are listed in Table I. Excluding the psychoactive constituents of the respective plants, most of the analytes were found in similar amounts in the two plants. The S. divinorum plant material used in this study demonstrated some variation even within the small sampling of the leaf material used for the smoking studies. The three samples analyzed for 2.20 ± 0.30, 3.82 ± 0.65 and 3.69 ± 0.04 mg salvinorin A per gram of plant material (n = 4 for each determination). The grand average of these determinations is 3.24 mg salvinorin A per gram of plant material or 0.324% of the dried plant material, which is near the average 0.245% salvinorin A content reported by Siebert (3). An 830 mg cigarette would then have ∼2.7 mg salvinorin A present. In the smoke, 133 μg of salvinorin A was delivered (∼5% yield) indicating significant conversion of salvinorin A to other components during combustion. Some evidence for this was seen by the presence of 217 μg of salvinorin B, which is a non-psychoactive hydrolysis product of salvinorin A. Additionally, the presence of small amounts (18 μg) of related salvinorin D or E was detected as indicated by their MW. Since salvinorins D and E can interconvert, the observed material is likely a mixture of D & E (9). Additionally, salvinorins D and E are partial hydrolysis products of salvinorin C, which is present in the plant (3); therefore, the salvinorin D or E observed here are likely combinations of amounts present in the plant and products of the combustion process in a manner comparable to the conversion of salvinorin B from salvinorin A.Considering that smoking S. divinorum as a cigarette is an effective method of achieving a psychoactive effect and salvinorin A is considered to be the sole active ingredient in the plant accounting for the effects (1), then the 133 μg of salvinorin A represents a high estimate of the minimal dosage needed to obtain a psychoactive effect from the drug. The actual amount of salvinorin A that needs to reach the brain would be significantly less due to the rapid metabolism of salvinorin A in vivo (10).

These results are in good agreement to the findings of the vaporization studies of Johnson et al. (4), where they determined that 210–420 μg using a vaporizer as the minimally effective dose in a 70 kg. It should be noted that this was the dose applied to the vaporizer and that the amount actually delivered to the subject was not determined. The vaporization method used (heating of salvinorin A in a glass vessel) might be expected to lead to less degradation of the salvinorin A than pyrolysis in a cigarette. Hence, our finding of 133 μg delivered the S. divinorum cigarette smoke compares well. Caveats to these studies are that first a single sample of S. divinorum was used and that amounts of salvinorin A can vary significantly in the plant (3) and second, the mode of simulated inhalation in the smoking apparatus may not fully replicate the inhalation pattern utilized by individuals smoking the plant material to achieve an effect. Therefore, while the numbers reported cannot be said to precisely define the average dose of salvinorin A delivered by the smoking route, it does present a value that should be within the range of delivered doses by this route."


The referenced scientific work at PubMed:

Krstenansky JL, Muzzio M. Analysis of the smoke of cigarettes containing Salvia divinorum. J Anal Toxicol. 2014 Sep;38(7):451-5. doi: 10.1093/jat/bku054. PubMed PMID: 24908261.


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Prof. Atanas G. Atanasov (Dr. habil., PhD)
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Plant Alkaloids for the Treatment of Depression



Abstract (as presented by the authors of the scientific work):

"Depression is a heterogeneous mood disorder that has been classified and treated in a variety of ways. Although, a number of synthetic drugs are being used as standard treatment for clinically depressed patients, but they have adverse effects that can compromise the therapeutic treatments and patient's compliance. Unlike, synthetic medications, herbal medicines are widely used across the globe due to their wide applicability and therapeutic efficacy associated with least side effects, which in turn has initiated the scientific research regarding the antidepressant activity. This review is mostly based on the literature of the last decade, aimed at exploring the preclinical profile of plant-based alkaloids (the abundant secondary metabolite) as an emerging therapy for depression."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Conclusion (as presented by the authors of the scientific work):

"Our review on the basis of available literature suggested that alkaloids could play a potential role as natural antidepressants. Keeping in mind their abundance in nature, the alkaloids could be an economical source of healing the depressive disorder. The available therapeutic agents fail to produced effect in all patients; approximately 30–40% failure has been reported to first-line antidepressant drugs accompanied by the very slow onset of action. Several alkaloids are in clinical practice and producing outstanding results in different therapeutic classes. These reported alkaloids though evoked antidepressant effects in various animal studies, but still deficient in clinical evidence. In conclusion, enough scientific evidence gathered in our review supported that the plant-based alkaloids can serve as leads for antidepressant drug discovery. It is key to subject these alkaloids to further clinical studies for efficacy, potency, and safety to ensure their clinical status."


The referenced scientific work at PubMed:

Perviz S, Khan H, Pervaiz A. Plant Alkaloids as an Emerging Therapeutic Alternative for the Treatment of Depression. Front Pharmacol. 2016 Feb 15;7:28. doi: 10.3389/fphar.2016.00028. Review. PubMed PMID: 26913004; PubMed Central PMCID: PMC4753303.


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Webmaster:

Prof. Atanas G. Atanasov (Dr. habil., PhD)
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