scholarly journals Interaction between Gut Microbiota and Curcumin: A New Key of Understanding for the Health Effects of Curcumin

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2499 ◽  
Author(s):  
Beatrice Scazzocchio ◽  
Luisa Minghetti ◽  
Massimo D’Archivio
Keyword(s):  
Gut Microbiota ◽  
Neurological Diseases ◽  
Curcuma Longa ◽  
Pharmacological Activities ◽  
Systemic Bioavailability ◽  
Microbiome Profile ◽  
Regulatory Effects ◽  
High Concentrations

Curcumin, a lipophilic polyphenol contained in the rhizome of Curcuma longa (turmeric), has been used for centuries in traditional Asian medicine, and nowadays it is widely used in food as dietary spice worldwide. It has received considerable attention for its pharmacological activities, which appear to act primarily through anti-inflammatory and antioxidant mechanisms. For this reason, it has been proposed as a tool for the management of many diseases, among which are gastrointestinal and neurological diseases, diabetes, and several types of cancer. However, the pharmacology of curcumin remains to be elucidated; indeed, a discrepancy exists between the well-documented in vitro and in vivo activities of curcumin and its poor bioavailability and chemical instability that should limit any therapeutic effect. Recently, it has been hypothesized that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of this polyphenol have been detected after oral administration. Consequently, it might be hypothesized that curcumin directly exerts its regulatory effects on the gut microbiota, thus explaining the paradox between its low systemic bioavailability and its wide pharmacological activities. It is well known that the microbiota has several important roles in human physiology, and its composition can be influenced by a multitude of environmental and lifestyle factors. Accordingly, any perturbations in gut microbiome profile or dysbiosis can have a key role in human disease progression. Interestingly, curcumin and its metabolites have been shown to influence the microbiota. It is worth noting that from the interaction between curcumin and microbiota two different phenomena arise: the regulation of intestinal microflora by curcumin and the biotransformation of curcumin by gut microbiota, both of them potentially crucial for curcumin activity. This review summarizes the most recent studies on this topic, highlighting the strong connection between curcumin and gut microbiota, with the final aim of adding new insight into the potential mechanisms by which curcumin exerts its effects.

scholarly journals Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2527 ◽  
Author(s):  
Bee Ling Tan ◽  
Mohd Esa Norhaizan
Keyword(s):  
Anticancer Activity ◽  
Molecular Mechanisms ◽  
Curcuma Longa ◽  
Adverse Outcomes ◽  
Chemotherapeutic Drugs ◽  
Biological Mechanisms ◽  
Pharmacological Activities ◽  
Underlying Mechanisms

Many chemotherapeutic drugs have been used for the treatment of cancer, for instance, doxorubicin, irinotecan, 5-fluorouracil, cisplatin, and paclitaxel. However, the effectiveness of chemotherapy is limited in cancer therapy due to drug resistance, therapeutic selectivity, and undesirable side effects. The combination of therapies with natural compounds is likely to increase the effectiveness of drug treatment as well as reduce the adverse outcomes. Curcumin, a polyphenolic isolated from Curcuma longa, belongs to the rhizome of Zingiberaceae plants. Studies from in vitro and in vivo revealed that curcumin exerts many pharmacological activities with less toxic effects. The biological mechanisms underlying the anticancer activity of co-treatment curcumin and chemotherapy are complex and worth to discuss further. Therefore, this review aimed to address the molecular mechanisms of combined curcumin and chemotherapy in the treatment of cancer. The anticancer activity of combined nanoformulation of curcumin and chemotherapy was also discussed in this study. Taken together, a better understanding of the implication and underlying mechanisms of action of combined curcumin and chemotherapy may provide a useful approach to combat cancer diseases.

scholarly journals Curcumin, Gut Microbiota, and Neuroprotection

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2426 ◽  
Author(s):  
Di Meo ◽  
Margarucci ◽  
Galderisi ◽  
Crispi ◽  
Peluso
Keyword(s):  
Neurological Diseases ◽  
Aqueous Solubility ◽  
Brain Health ◽  
Active Metabolites ◽  
Pharmacological Activities ◽  
Naturally Occurring ◽  
The Central Nervous System ◽  
High Concentrations

Curcumin, a nontoxic, naturally occurring polyphenol, has been recently proposed for the management of neurodegenerative and neurological diseases. However, a discrepancy exists between the well-documented pharmacological activities that curcumin seems to possess in vivo and its poor aqueous solubility, bioavailability, and pharmacokinetic profiles that should limit any therapeutic effect. Thus, it is possible that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of curcumin are present after oral administration. Indeed, a new working hypothesis that could explain the neuroprotective role of curcumin despite its limited availability is that curcumin acts indirectly on the central nervous system by influencing the “microbiota–gut–brain axis”, a complex bidirectional system in which the microbiome and its composition represent a factor which preserves and determines brain “health”. Interestingly, curcumin and its metabolites might provide benefit by restoring dysbiosis of gut microbiome. Conversely, curcumin is subject to bacterial enzymatic modifications, forming pharmacologically more active metabolites than curcumin. These mutual interactions allow to keep proper individual physiologic functions and play a key role in neuroprotection.

scholarly journals Berberine-Loaded Carboxylmethyl Chitosan Nanoparticles Ameliorate DSS-Induced Colitis and Remodel Gut Microbiota in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Luqing Zhao ◽  
Xueying Du ◽  
Jiaxin Tian ◽  
Xiuhong Kang ◽  
Yuxin Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Drug Loading ◽  
Chitosan Nanoparticles ◽  
Triggered Release ◽  
Release Studies ◽  
Anti Inflammatory ◽  
High Concentrations ◽  
Recurrent Inflammation

Inflammatory bowel disease (IBD) is a refractory disorder characterized by chronic and recurrent inflammation. The progression and pathogenesis of IBD is closely related to oxidative stress and irregularly high concentrations of reactive oxygen species (ROS). A new oxidation-responsive nano prodrug was constructed from a phenylboronic esters-modified carboxylmethyl chitosan (OC-B) conjugated with berberine (BBR) that degrades selectively in response to ROS. The optimized micelles exhibited well-controlled physiochemical properties and stability in a physiological environment. OC-B-BBR micelles could effectively encapsulate the anti-inflammatory drug berberine and exhibit ideal H2O2-triggered release behavior as confirmed by in vitro drug loading and release studies. The in vivo anti-inflammatory effect and regulation of gut microbiota caused by it were explored in mice with colitis induced by dextran sodium sulfate (DSS). The results showed that OC-B-BBR significantly ameliorated colitis symptoms and colon damage by regulating the expression levels of IL-6 and remodeling gut microbiota. In summary, this study exhibited a novel BBR-loaded Carboxylmethyl Chitosan nano delivery system which may represent a promising approach for improving IBD treatment.

Probing the 14-3-3 Isoform-Specificity Profile of Interactions Stabilized by Fusicoccin A

2020 ◽  
Author(s):  
James Frederich ◽  
Ananya Sengupta ◽  
Josue Liriano ◽  
Ewa A. Bienkiewicz ◽  
Brian G. Miller
Keyword(s):  
Protein Interactions ◽  
Neurological Diseases ◽  
Adapter Proteins ◽  
Protein Protein Interactions ◽  
Specific Expression ◽  
Individual Client ◽  
Isoform Specificity ◽  
Fusicoccin A

Fusicoccin A (FC) is a fungal phytotoxin that stabilizes protein–protein interactions (PPIs) between 14-3-3 adapter proteins and their phosphoprotein interaction partners. In recent years, FC has emerged as an important chemical probe of human 14-3-3 PPIs implicated in cancer and neurological diseases. These previous studies have established the structural requirements for FC-induced stabilization of 14-3-3·client phosphoprotein complexes; however, the effect of different 14-3-3 isoforms on FC activity has not been systematically explored. This is a relevant question for the continued development of FC variants because there are seven distinct isoforms of 14-3-3 in humans. Despite their remarkable sequence and structural similarities, a growing body of experimental evidence supports both tissue-specific expression of 14-3-3 isoforms and isoform-specific functions <i>in vivo</i>. Herein, we report the isoform-specificity profile of FC <i>in vitro</i>using recombinant human 14-3-3 isoforms and a focused library of fluorescein-labeled hexaphosphopeptides mimicking the C-terminal 14-3-3 recognition domains of client phosphoproteins targeted by FC in cell culture. Our results reveal modest isoform preferences for individual client phospholigands and demonstrate that FC differentially stabilizes PPIs involving 14-3-3s. Together, these data provide strong motivation for the development of non-natural FC variants with enhanced selectivity for individual 14-3-3 isoforms.

Novel Phytochemical Constituents and their Potential to Manage Diabetes

2020 ◽  
Vol 26 ◽  
Author(s):  
Shaik Ibrahim Khalivulla ◽  
Arifullah Mohammed ◽  
Kokkanti Mallikarjuna
Keyword(s):  
Natural Products ◽  
Large Population ◽  
World Health ◽  
In Vivo Studies ◽  
Antidiabetic Activity ◽  
Therapeutic Drug ◽  
Pharmacological Activities ◽  
Chemical Structures

Background: Diabetes is a chronic disease affecting a large population worldwide and stands as one of the major global health challenges to be tackled. According to World Health Organization, about 400 million are having diabetes worldwide and it is the seventh leading cause of deaths in 2016. Plant based natural products had been in use from ancient time as ethnomedicine for the treatment of several diseases including diabetes. As a result of that, there are several reports on plant based natural products displaying antidiabetic activity. In the current review, such antidiabetic potential compounds reported from all plant sources along with their chemical structures are collected, presented and discussed. This kind of reports are essential to pool the available information to one source followed by statistical analysis and screening to check the efficacy of all known compounds in a comparative sense. This kind of analysis can give rise to few numbers of potential compounds from hundreds, whom can further be screened through in vitro and in vivo studies, and human trails leading to the drug development. Methods: Phytochemicals along with their potential antidiabetic property were classified according to their basic chemical skeleton. The chemical structures of all the compounds with antidiabetic activities were elucidated in the present review. In addition to this, the distribution and their other remarkable pharmacological activities of each species is also included. Results: The scrutiny of literature led to identification of 44 plants with antidiabetic compounds (70) and other pharmacological activities. For the sake of information, the distribution of each species in the world is given. Many plant derivatives may exert antidiabetic properties by improving or mimicking the insulin production or action. Different classes of compounds including sulfur compounds (1-4), alkaloids (5-11), phenolic compounds (12-17), tannins (18-23), phenylpropanoids (24-27), xanthanoids (28-31), amino acid (32), stilbenoid (33), benzofuran (34), coumarin (35), flavonoids (36-49) and terpenoids (50-70) were found to be active potential compounds for antidiabetic activity. Of the 70 listed compounds, majorly 17 compounds are from triterpenoids, 13 flavonoids and 7 are from alkaloids. Among all the 44 plant species, maximum number (7) of compounds are reported from Lagerstroemia speciosa followed by Momordica charantia (6) and S. oblonga with 5 compounds. Conclusion: This is the first paper to summarize the established chemical structures of phytochemicals that have been successfully screened for antidiabetic potential and their mechanisms of inhibition. The reported compounds could be considered as potential lead molecules for the treatment of type-2 diabetes. Further, molecular and clinical trials are required to select and establish the therapeutic drug candidates.

Ethnomedicinal uses, Phytochemistry and Pharmacological Aspects of the Genus Berberis Linn: A Comprehensive Review

2020 ◽  
Vol 23 ◽  
Author(s):  
Roohi Mohi-ud-din ◽  
Reyaz Hassan Mir ◽  
Prince Ahad Mir ◽  
Saeema Farooq ◽  
Syed Naiem Raza ◽  
...  
Keyword(s):  
Chemical Constituents ◽  
Pharmacological Activities ◽  
Traditional Use ◽  
Comprehensive Review ◽  
Wide Range ◽  
Anti Cancer ◽  
Comprehensive Survey ◽  
Ethnomedicinal Uses

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. Objective: The present review is focussed to summarize and collect the updated review of information of Genus Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory both in vitro & in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.

Nyctanthes Arbor-Tristis and its Role in the Alleviation of Arthritic Pain: A Review

2020 ◽  
Vol 16 (8) ◽  
pp. 1147-1156
Author(s):  
Ruchi Singh ◽  
Syed M. Hasan ◽  
Amit Verma ◽  
Sanjay K. Panda
Keyword(s):  
Research Work ◽  
Plant Distribution ◽  
Pharmacological Activities ◽  
Whole Plant ◽  
Modern Drug ◽  
Active Chemical ◽  
Drug Synthesis ◽  
New Compounds

Background: A plant is a reservoir of potentially useful active chemical entities which act as drugs as well as intermediates for the discovery of newer molecules and provide newer leads for modern drug synthesis. The demand for new compounds in the field of medicine and biotechnology is centuries old and with a rise in chronic diseases and resistance to existing drugs in the field of anti-infective agents, the chemicals obtained from plant sources have been an area of attraction. The whole plant has possessed multiple pharmacological activities. This is scientifically established by in-vivo and in-vitro studies. Methods: Various electronic databases such as PubMed, Science Direct, Scopus and Google were searched to collect the data of the present review. All the collected information is categorized into different sections as per the aim of the paper. Results: Fifty-six research and review papers have been studied and were included in this review article. After a detailed study, we provide a significant description of various phytochemicals present in Nyctanthes arbor-tristis Linn., which is responsible for various pharmacological activities. Twenty of studied articles gives a general introduction and ethnobotanical information about the plant, two papers contained microscopic detail of leaf and fruit. Twenty papers contained information about the phytoconstituents present in different parts of Nyctanthes arbor-tristis plant and fourteen articles reported pharmacological activities like antioxidant, anti-inflammatory, antiarthritic, antimicrobial and immunobiotic activity. Conclusion: This review explores the published research work comprising the ethnobotanical description of the subjected plant, distribution, phytochemical profile, and arthritis-related pharmacological activities.

scholarly journals Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets

2020 ◽  
Vol 318 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Richard A. Jacobson ◽  
Kiedo Wienholts ◽  
Ashley J. Williamson ◽  
Sara Gaines ◽  
Sanjiv Hyoju ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Healing Process ◽  
Abdominal Sepsis ◽  
Infectious Complications ◽  
Fibrinolytic System ◽  
Clinical Safety ◽  
High Concentrations ◽  
Clinically Significant

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

scholarly journals Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review

2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell
Keyword(s):  
Systematic Review ◽  
Tissue Engineering ◽  
Collagen Type I ◽  
The Body ◽  
Pool Data ◽  
Type I ◽  
High Concentrations ◽  
Increased Strength

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.

scholarly journals The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Zhicheng Zheng ◽  
Peiyu Liang ◽  
Baohua Hou ◽  
Xin Lu ◽  
Qianwen Ma ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neurological Diseases ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Sequencing Data ◽  
Migration Ability ◽  
Dpp4 Inhibitor ◽  
Phenotypic Transformation

Abstract Background Accumulating evidence suggests that disease-associated microglia (DAM), a recently discovered subset of microglia, plays a protective role in neurological diseases. Targeting DAM phenotypic transformation may provide new therapeutic options. However, the relationship between DAM and epilepsy remains unknown. Methods Analysis of public RNA-sequencing data revealed predisposing factors (such as dipeptidyl peptidase IV; DPP4) for epilepsy related to DAM conversion. Anti-epileptic effect was assessed by electroencephalogram recordings and immunohistochemistry in a kainic acid (KA)-induced mouse model of epilepsy. The phenotype, morphology and function of microglia were assessed by qPCR, western blotting and microscopic imaging. Results Our results demonstrated that DPP4 participated in DAM conversion and epilepsy. The treatment of sitagliptin (a DPP4 inhibitor) attenuated KA-induced epilepsy and promoted the expression of DAM markers (Itgax and Axl) in both mouse epilepsy model in vivo and microglial inflammatory model in vitro. With sitagliptin treatment, microglial cells did not display an inflammatory activation state (enlarged cell bodies). Furthermore, these microglia exhibited complicated intersections, longer processes and wider coverage of parenchyma. In addition, sitagliptin reduced the activation of NF-κB signaling pathway and inhibited the expression of iNOS, IL-1β, IL-6 and the proinflammatory DAM subset gene CD44. Conclusion The present results highlight that the DPP4 inhibitor sitagliptin can attenuate epilepsy and promote DAM phenotypic transformation. These DAM exhibit unique morphological features, greater migration ability and better surveillance capability. The possible underlying mechanism is that sitagliptin can reduce the activation of NF-κB signaling pathway and suppress the inflammatory response mediated by microglia. Thus, we propose DPP4 may act as an attractive direction for DAM research and a potential therapeutic target for epilepsy.

Sign in / Sign up

Export Citation Format

Share Document