Plant Extracts to Enhancing Intestinal Barrier Function in Fattening lambs: A Review.

The present study investigated the protective effects of emodin on intestinal epithelial tight junction (TJ) barrier integrity in cecal ligation and puncture (CLP)-induced septic rats and its possible mechanisms of action. Healthy male Sprague-Dawley rats were randomly divided into three groups (n=20 per group): Sham group, CLP group and CLP + emodin group. Animals were sacrificed at 12 and 24 h after the model was established. Abdominal aortic blood and specimens of the ileum were harvested for analysis. The histopathological changes in intestinal mucosa and the ultrastructures of intestinal epithelial cells were investigated using light microscopy and transmission electron microscopy. The integrity of the intestinal barrier was assessed by examining plasma diamine oxidase (DAO) levels and the ratio of urine lactulose to mannitol (L/M). The levels of the intestinal TJ proteins claudin-3, zonula occludens (ZO)-1 and occludin were detected using immunohistochemistry, western blotting and reverse transcription-quantitative PCR. The results showed that the pathological damage to intestinal mucosa and the intestinal tissue injury score in the CLP + emodin group were significantly reduced compared to those of the CLP group, and the differences were more obvious at 24 h compared with 12 h. DAO activity and the L/M ratio in the emodin pre-treatment group decreased significantly at 24 h compared with the CLP groups. The protein and mRNA levels of the TJ proteins claudin-3, ZO-1 and occludin in the emodin pre-treatment groups at 12 and 24 h were increased, while occludin mRNA level was found to be decreased compared with the CLP groups. The present study suggested that emodin may significantly reduce the damage to the intestinal epithelial barrier in sepsis, inhibit intestinal barrier permeability and protect intestinal barrier integrity. Emodin may protect intestinal barrier integrity by elevating expression levels of the TJ proteins claudin-3, ZO-1 and occludin in CLP rats.

Curcumin suppresses angiogenesis, cell proliferation and induces apoptosis in an in vitro model of endometriosis

ObjectivePhytoestrogens display an array of pharmacologic properties, and in recent years investigation of their potential as anticancer agents has increased dramatically. In this article we review the published literature related to phytoestrogens and breast cancer as well as suggest the possible mechanisms that may underlie the relationship between phytoestrogens and breast cancer.Data sourcesElectronic searches on phytoestrogens and breast cancer were performed on MEDLINE and EMBASE in June 2007. No date restriction was placed on the electronic search.Data extractionWe focused on experimental data from published studies that examined the characteristics of phytoestrogens using in vivo or in vitro models. We also include human intervention studies in this review.Data synthesisWe evaluated evidence regarding the possible mechanisms of phytoestrogen action. Discussions of these mechanisms were organized into those activities related to the estrogen receptor, cell growth and proliferation, tumor development, signaling pathways, and estrogen-metabolizing enzymes.ConclusionsWe suggest that despite numerous investigations, the mechanisms of phytoestrogen action in breast cancer have yet to be elucidated. It remains uncertain whether these plant compounds are chemoprotective or whether they may produce adverse outcomes related to breast carcinogenesis.

Tumor necrosis factor alpha-induced receptor 1 signaling in alcoholic liver disease: A gut reaction?

Colorectal cancer (CRC) is a heterogeneous disease of the colon and rectum. In Indonesia, CRC has the fourth highest cancer incidence, with about 30,000 new cases and causing around 16,000 deaths per year. Numerous studies have shown the benefits of using simvastatin and Annona muricata (A. muricata) leaf extract to promote cytotoxic effects in CRC cells. This systematic review aimed to evaluate the effects and the possible molecular mechanisms of actions used by simvastatin and A. muricata leaf extract to exert anti-cancer effects in CRC cells. We synthesized published studies on the effect of simvastatin and A. muricata leaf extract in in vitro and in vivo CRC studies, and highlighted the potential application of simvastatin and A. muricata leaf extract in combination with other anti-cancer treatments. This systematic review was written in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Simvastatin and A. muricata leaf extract were shown to suppress CRC cell growth and proliferation and generate a synergistic effect when combined with other anti-cancer treatments. Several possible mechanisms of actions of simvastatin include bone morphogenetic protein (BMP) pathway and mevalonate pathway activation, ERKs inactivation, and regulation of the yes-associated protein 1 (YAP1), while for A. muricata leaf extract, possible mechanisms of actions include intrinsic apoptosis pathway activation, cytochrome c-mediated apoptosis, mitochondria-mediated apoptosis, and programmed cell death initiation. Further experimental evidence is needed to determine the specific mechanisms on how simvastatin and A. muricata leaf extract induce anti-cancer effects against CRC cells.

Introduction. Modern chemotherapy widely considers the role of antioxidant and pro-oxidant methods in the treatment of oncologic pathologies. The use of agents that cause an increase of ROS is a relevant way to destroy tumors. At the same time, there is evidence of the ability of some antioxidants to lead to the cancer cells apoptosis through the generation of free radical forms of oxygen due to disruption of cellular homeostasis. The combination of the «Ecolum» biosensor using technique, antiradical activity data, and information about the cytotoxicity of compounds used in the study allows us to consistently conduct low-cost screening of as antioxidant, as antiradical activities and potentially reduce the required number of expensive cytotoxicity determinations using tumor cells.Aim. The main target of our work is the evaluation of antioxidant and cytotoxic activities of 1,3-dioxolane derivatives of imidazole using antioxidant, antiradical and cytotoxicity tests in vitro.Materials and methods. To carry out this study, 1,3-dioxolane derivatives of imidazole were obtained. The antiradical tests was performed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Antioxidant properties were assessed within the Ecolum biosensor in the state of oxidative stress. Cytotoxic activity was assessed in GIST-T1 cell culture using the MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide).Results and discussion. Data from studies of the antioxidant activity of substances using the «Ecolum» biosensor showed varying degrees of damage to the biosensor in the absence of antioxidant action. The antiradical potential, initially used to reveal a possible mechanism of antioxidant action, actually demonstrated a possible mechanism of toxic action of substance 2c due to its antiradical effect comparable to the standard (Trolox), but the substance has the highest cytotoxicity. However, the properties of substance 2a shows that the direct correlation discussed earlier is not found in all cases.Conclusion. The asessment of the antioxidant properties and cytotoxic activity of 1,3-dioxolane derivatives of imidazole demonstrated the relevance of further searching for connections between the results of substances binding with the Ecolum biosensor under conditions of oxidative stress, their antiradical potential and cytotoxic properties. This combination of tests will potentially reduce the cost of screening through the use of an available biosensor, establish a possible mechanism of action aimed at redox balance, and confirm previously obtained data through the use of tumor cell culture.

The increasing incidence of drug- resistant pathogens raises an urgent need to identify and isolate new bioactive compounds from medicinal plants using standardized modern analytical procedures. Medicinal plant-derived compounds could provide novel straightforward approaches against pathogenic bacteria. This review explores the antimicrobial activity of plant-derived components, their possible mechanisms of action, as well as their chemical potential. The focus is put on the current challenges and future perspectives surrounding medicinal plants antimicrobial activity. There are some inherent challenges regarding medicinal plant extracts and their antimicrobial efficacy. Appropriate and optimized extraction methodology plant species dependent leads to upgraded and selective extracted compounds. Antimicrobial susceptibility tests for the determination of the antimicrobial activity of plant extracts may show variations in obtained results. Moreover, there are several difficulties and problems that need to be overcome for the development of new antimicrobials from plant extracts, while efforts have been made to enhance the antimicrobial activity of chemical compounds. Research on the mechanisms of action, interplay with other substances, and the pharmacokinetic and/or pharmacodynamic profile of the medicinal plant extracts should be given high priority to characterize them as potential antimicrobial agents.

Effects of Hydrogen Sulfide on Erectile Function and Its Possible Mechanism(s) of Action

Background and PurposePeripheral tissue damage and diseases could lead to persistent pain beyond possible resolution suggestive of disease-promoting condition which gives rise to chronic pain. The inability of current medications to manage some chronic inflammatory and painful conditions necessitate the need for better treatment options. Natural products have been a veritable source for the discovery of more efficacious and safer therapeutics. Cajanus cajan (L) Millsp, (Fabaceae) is used in traditional African medicines for the treatment of painful, gut disturbance and inflammatory conditions. Hence, the current study aims to investigate the anti-inflammatory and antinociceptive actions of the ethanol seed extract of Cajanus cajan (CC) in rodents and possible mechanisms of action. MethodsHigh performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was used to identify 8 major flavonoids in CC. Antinociceptive activity was investigated using the acetic acid-induced writhing reflex, biphasic formalin-induced flinching behaviour and supraspinal hot plate-evoked nociception in mice. Carrageenan-induced rat paw oedema test was used to evaluate the anti-inflammatory action of CC in rats. Possible mechanism of antinociception and anti-inflammatory actions were examined using both in vivo model and molecular docking procedures against µ-opioid receptor (MOR), cyclooxygenase-2 (COX-2) and phospholipase A2 (PLA2) proteins, respectively. ResultsThe chromatographic procedure qualitatively and quantitatively confirmed the presence of rutin, quercetin, gallic acid, luteolin, pinostrobin, BiochaninA, formononetin and apigenin in CC. The in vivo nociceptive assay, showed that CC (50, 100, or 200 mg/kg, p.o.) significantly decreased mean number of writhing reflex with peak effect at 50 mg/kg (72% inhibition) when compared with vehicle control in mouse writhing test. Similarly, the biphasic formalin-induced nociception was significantly reduced by CC (50 mg/kg) with 24.61 and 66.73% inhibition of nociceptive reactions in both the early and late phases of formalin-induced inflammatory pain, respectively. In addition, CC significantly increased supraspinal thermally mediated pain threshold with maximum possible effects of 42.25 and 52.16% at CC 50 and 100 mg/kg, respectively, in hot-plate test. Similarly, CC100mg/kg caused time course inhibition of carrageenan-induced paw oedema in rat with peak effect (65.78%, CC 100 mg/kg; 6 h). Interestingly, the antinociceptive action of CC was blocked by the pre-treatment of mice with l-NG-nitro arginine methyl ester (L-NAME) or naloxone. The molecular docking analysis revealed prominent interactions of pinostrobin, physcion and lupeol with MOR, COX-2, and PLA2, respectively. ConclusionFindings from this study showed that Cajanus cajan seeds extract possesses anti-nociceptive and anti-inflammatory through inhibition of inflammatory mediators (PLA2/COX-2) and activation of opioidergic signalling.

Background/Objectives: Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii. The parasite infection in humans continues to rise due to an increasing seroprevalence rate in domestic and wild warm-blooded animals that serve as a major reservoir of the parasite. There are fewer drugs available for the treatment of toxoplasmosis. However, these drugs are limited in efficacy against tachyzoites and bradyzoites. Also, there are clinical side effects and geographical barriers to their use, especially in immunocompromised patients, children, and pregnant women. Tannins, a class of natural products, are known to have antimicrobial properties. However, little is known about the effects of Corilagin (CG) and Punicalagin (PU), which are classified as tannins, on T. gondii growth and their possible mechanism of action in vitro. We hypothesize that CG and PU could inhibit T. gondii growth in vitro and cause mitochondria membrane disruption via oxidative stress. Methods: Here, we investigated the anti-T. gondii activity of the two named tannins using a fluorescent-based reporter assay. Results: The 50% effective concentrations (EC50s) values for CG and PU that inhibited T. gondii parasites growth in vitro were determined to be 3.09 and 19.33 µM, respectively. Pyrimethamine (PY) was used as a standard control which gave an EC50 value of 0.25 µM. Interestingly, CG and PU were observed to cause high reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX) production in tachyzoites. This resulted in a strong mitochondria membrane potential (MMP) disruption in T. gondii tachyzoites. Conclusions: Therefore, the possible mechanism(s) of action of CG and PU against T. gondii is associated with the disruption of the mitochondria redox biology. Thus, the high ROS and MitoSOX produced as a result of these compounds created high oxidative stress, leading to mitochondrial dysfunction.

Silybin, a flavonolignan extracted from the seeds of the plant species Silybum marianum (L.) Gaertn., has a variety of pharmacological activities, including antimicrobial activity against several microorganisms of clinical interest. This review analyzes the existing studies on silybin's antimicrobial activity and possible mechanisms of action. Silybin has been shown to inhibit the growth of Gram-positive and Gram-negative bacteria, as well as some fungi, viruses, and protozoa. In general, possible mechanisms of antimicrobial action include the inhibition of efflux pumps, prevention of biofilm formation, reduction of the expression of virulence factors, induction of apoptosis-like effects, and plasma membrane damage, as well as the inhibition of nucleic acid and protein synthesis. Silybin has been shown to have synergistic effects when combined with conventional antibiotics against both drug-sensitive and drug-resistant microorganisms. However, the low bioavailability observed for this flavonolignan has been a challenge to its clinical use. In this context, nanotechnology has been used to increase silybin's bioavailability while enhancing its antimicrobial activity. Furthermore, certain structural modifications have been able to enhance its antimicrobial activity in comparison to that of the natural molecule. Overall, this review provides insights into the scientific understanding of the mechanism of action of silybin and its desired properties for the effective treatment of infections.

The antihyperglycemic and hypolipidemic activities of Helicteres isora Linn. (Sterculiaceae) root extracts were investigated in alloxan-induced diabetic rats and a possible mechanism of the blood glucose lowering action was studied. Alloxan-induced diabetic rats experienced 69.13 and 51.14%, 22.60 and 21.89%, 30.12 and 19.96%, and 50.05 and 34.29% reduction in blood glucose, total cholesterol, triglycerides, and urea levels following oral administration of butanol and aqueous ethanol extracts of H. isora root, respectively, at 250 mg/kg for 10 days. The beneficial effects of these extracts were supported by evidence from histological examinations of the liver, pancreas, and kidney. Following the treatment with both extracts, the degenerative changes caused by alloxan in pancreatic cells were restored, particularly with the butanol extract. Histological examination convincingly showed the restoration of pancreatic islets, kidney glomeruli, and liver to its normal size. These results suggest that H. isora roots possess antidiabetic principles and can be useful for treatment of diabetes.

GABAergic effect of valeric acid from Valeriana wallichii in amelioration of ICV STZ induced dementia in rats

Synergistic effect of plant extract coupled silver nanoparticles in various therapeutic applications- present insights and bottlenecks

Background: Depression is a crippling mental disorder with high prevalence around the world. The available clinical antidepressants have been effective to a certain degree, and different side effects have limited their application. This leads to the necessity of finding new treatments. Herbal plants are a substantial source of new drug leads. Terpenoid compounds are secondary metabolites representing an enormous category of structures found commonly in plants either as aglycones or attached to sugar moieties. These phytochemicals have been extensively studied for their various biological effects, and several have been investigated for potential therapeutic effects in the treatment of depression. Aim: This review aims to highlight the current knowledge on some terpenoids and triterpenoid saponins as potential antidepressant agents and their mechanisms of action, which may provide a better understanding of the potential antidepressant-like effects of these compounds and lead to the development of auspicious molecules with high efficiency and low side effects for depressive disorders treatment. Methods: A total of 16 plants containing antidepressant agents are reviewed in this article. 9 terpenoids and 23 triterpenoid saponins compounds have been reported to becommonly found in plant extracts, indicating potential use for depression. To enhance the datum of this review, the mechanism of action for the candidate compounds has been predicted via functional enrichment analysis. Results: The behavioural and neurochemical effects, as well as the possible mechanisms of action, have been evaluated in rodents by different predictive models of depression, mainly the acute stress models of the forced swimming test (FST) and tail suspension test (TST). The involved mechanisms include enhancing monoamine neurotransmitters, ameliorating brain-derived neurotrophic factor (BDNF), and normalizing the hypothalamus-pituitary-adrenal (HPA) axis. Preclinical studies support the potential antidepressant activities of some terpenoid compounds. Furthermore, the functional enrichment analysis has confirmed the previous pre-clinical findings and predicted further mechanisms of action, including cellular calcium ion homeostasis, cellular response to dopamine, endocrine resistance, and regulating GABAergic, serotonergic, glutamatergic, and dopaminergic synapse, bedsides neurotransmitter reuptake. Conclusion: Terpenoids and triterpenoid saponins provide a large number of natural compounds. This review sheds light on terpenoids and triterpenoid saponins compounds with antidepressantlike activity and their potential mechanisms of action. However, more evaluations are required to confirm that these compounds are promising for discovering antidepressant drugs.