Psoriasis: A review of the role of serotonergic system

Psoriasis, a chronic inflammatory skin disease, is not yet curable, and its precise causes remain unclear. Nevertheless, several lines of evidence support that psoriasis is a multifactorial disease. Because psoriasis occurs in connection with stress and mood disorders, the genes in serotonergic system may be involved in psoriasis with regard to etiology and pathogenesis. Such molecular impacts supported by scientific evidence on serotonergic gene expression changes and genetic polymorphisms have been increasingly highlighted. The serotonergic system has also received considerable attention as a potential target for the therapy of psoriasis. Here, we summarize the current knowledge about role of genes in serotonergic system in psoriasis and point out possible directions of future studies

Effect of Gymnema inodorum on postprandial peak plasma glucose levels in healthy human

Gymnema inodorum (GI), a vegetable widely used in a Northern Thai food, is known for not only its health nourishing effect, but also its hypoglycemic effect. But no scientific evidence on the hypoglycemic effect of GI has ever been reported in human. In this study, the effect of GI consumptionon peak plasma glucose concentrations in healthy subjects was investigated. Either oral glucose load (75 g) or standard meal was given to the subjects with respect to the presence or absence of GI consumption and postprandial peak glucose levels were compared. When GI was consumed, 15 min after oral glucose load, the glucose concentration with GI was significantly lower (130 ± 32 vs. 145 ± 27 mg/dl, p < 0.05; N = 73). Doubling dose of GI showed much greater decrease in peak blood glucoseconcentration than that of the single dose (108 ± 15 vs. 130 ± 32 mg/dl, p < 0.05). When standard meal was used instead of oral glucose load, similar hypoglycemic effect was observed in GI group; 16 out of 20 subjects had a lowered peak glucose concentration (129 ± 27 vs. 147 ± 39 mg/dl, p < 0.05). In order to evaluate the impact of long term GI consumption on plasma glucose concentration and liver function, fasting plasma glucose and liver function test (AST, ALT, GGT and ALP) were monitored at days 0, 2, 4, 7, 14, 21 and 28. The results showed no change in both fasting plasma glucose and liver enzymes. To envisage the mechanism of this hypoglycemic effect, GI leaves were extracted with various solvents and tested for insulinotropic property in INS-1 cells as well as the determination of its inhibition on aglucosidase activity. Neither increase in insulin level nor inhibition of a-glucosidase enzyme wasobserved, suggesting that the hypoglycemic effect of GI is involved with other mechanisms than the activation of beta cell or enzymatic inhibition of carbohydrate absorption

Modulatory effects of Thai medicinal plant extract on proinflammatory cytokines-induced apoptosis in human keratinocyte HaCaT cells

It has been experimentally proven that proinflammatory cytokines, interferon (IFN)-y and tumor necrosis factor (TNF)-a are able to synergistically induce apoptosis in HaCaT keratinocyte cells. The present study aimed to elucidate modulatory effects of ethanolic extracts derived from Thai traditional medicinal plants on IFN-y/TNF-a-caused HaCaT apoptosis and correlate with their natural phenolic content. Using 3-(4-5 dimethylthiozol-2-yl) 2-5 diphenyl-tetrazolium bromide (MTT) assay, we found that herbal extracts derived from members of the Acanthaceae family, Rhinacanthus nasutus (L.) Kurz (0.1, 1 and 10 μg/ml) and Clinacanthus nutans (Burm.f.) Lindau (1 and 100 μg/ml), significantly inhibited the IFN-y/TNF-a- induced HaCaT apoptosis, while members of the Zingiberaceae family, Curcuma longa L. and Alpinia galanga (L.) Willd, significantly enhanced apoptosis when a concentration of 100 μg/ml was used. Furthermore, the ethanolic plant extracts were found to possess different amounts of total phenolics ranging from 1.64 to 10.04 mg GAE/g as determined using Folin-Ciocalteu assay. The richest phenolic sources were R. nasutus (10.04 ± 1.12 mg GAE/g) and C. longa (7.49 ± 0.50 mg GAE/g), whereas the least phenolic source was Centella asiatica (1.64 ± 0.84 mg GAE/g). Taken together, we found certain modulatory effects of Thai medicinal extracts on IFN-y/TNF-a-induced apoptosis in HaCaT cells, but these findings might not be directly correlated with their natural phenolic  content. Therefore, further investigations on different types of natural phenolic contents in these Thai medicinal extracts and their relevant molecular mechanisms in keratinocytes, should be carried out in the near future.Key words: Interferon, tumor necrosis factor, Thai medicinal herbs, apoptosis, phenolics, human keratinocytes

Assessment of anti-TNF-α activities in keratinocytes expressing inducible TNF- α: A novel tool for anti-TNF-α drug screening

© 2016 Udommethaporn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine important in normal and pathological biological processes. Newly synthesized pro-TNF-α is expressed on the plasma membrane and cleaved to release soluble TNF-α protein: both are biologically active. Secreted TNF-α signals through TNF receptors and the membrane-bound TNF-α acts by cell contact-dependent signaling. Anti-TNF-α antibodies have been used effectively for treatment of chronic inflammation, however with adverse side effects. Thus, there is a need for new anti-TNF-α small molecule compounds. Anti-TNF-α activity assays involve treatment of keratinocytes with exogenous TNF-α before or after anti-TNF-α incubation. However, this model fails to address the dual signaling of TNF-α. Here we describe a Doxycycline (Dox)-inducible TNF-α (HaCaT-TNF-α) expression system in keratinocytes. Using this in-vitro model, we show cell inhibition and induced expression of pro-inflammatory cytokines and markers, including IL-1β, IL-6, IL-8, NF-êB1, and KRT-16, similar to cells treated with exogenous TNF-α. Sufficient secreted TNF-α produced also activated IL-1β and IL-8 expression in wt HaCaT cells. Importantly, stimulated expression of IL-1β and IL-8 in HaCaT-TNF-α were blocked by Quercetin, a flavanol shown to possess anti-TNF-α activities. This novel in vitro cell model provides an efficient tool to investigate the dual signaling of TNF-α. Importantly, this model provides an effective, fast, and simple screening for compounds with anti-TNF-α activities for chronic inflammatory disease therapies

Acid-base fractions separated from Streblus asper leaf ethanolic extract exhibited antibacterial, antioxidant, anti-acetylcholinesterase, and neuroprotective activities

© 2018 The Author(s). Background: Streblus asper is a well-known plant native to Southeast Asia. Different parts of the plant have been traditionally used for various medicinal purposes. However, there is very little scientific evidence reporting its therapeutic benefits for potential treatment of Alzheimer's disease (AD). The study aimed to evaluate antibacterial, antioxidant, acetylcholinesterase (AChE) inhibition, and neuroprotective properties of S. asper leaf extracts with the primary objective of enhancing therapeutic applications and facilitating activity-guided isolation of the active chemical constituents. Methods: The leaves of S. asper were extracted in ethanol and subsequently fractionated into neutral, acid and base fractions. The phytochemical constituents of each fraction were analyzed using GC-MS. The antibacterial activity was evaluated using a broth microdilution method. The antioxidant activity was determined using DPPH and ABTS radical scavenging assays. The neuroprotective activity against glutamate-induced toxicity was tested on hippocampal neuronal HT22 cell line by evaluating the cell viability using MTT assay. The AChE inhibitory activity was screened by thin-layer chromatography (TLC) bioautographic method. Results: The partition of the S. asper ethanolic leaf extract yielded the highest mass of phytochemical constitutions in the neutral fraction and the lowest in the basic fraction. Amongst the three fractions, the acidic fraction showed the strongest antibacterial activity against gram-positive bacteria. The antioxidant activities of three fractions were found in the order of acidic > basic > neutral, whereas the decreasing order of neuroprotective activity was neutral > basic > acidic. TLC bioautography revealed one component in the neutral fraction exhibited anti-AChE activity. While in the acid fraction, two components showed inhibitory activity against AChE. GC-MS analysis of three fractions showed the presence of major phytochemical constituents including terpenoids, steroids, phenolics, fatty acids, and lipidic plant hormone. Conclusions: Our findings have demonstrated the therapeutic potential of three fractions extracted from S. asper leaves as a promising natural source for neuroprotective agents with additional actions of antibacterials and antioxidants, along with AChE inhibitors that will benefit in the development of new natural compounds in therapies against AD

Mushroom-derived bioactive compounds potentially serve as the inhibitors of SARS-CoV-2 main protease: An in silico approach

Background and aim Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become the world pandemic. There is a race to develop suitable drugs and vaccines for the disease. The anti-HIV protease drugs are currently repurposed for the potential treatment of COVID-19. The drugs were primarily screened against the SARS-CoV-2 main protease. With an urgent need for safe and effective drugs to treat the virus, we have explored natural products isolated from edible and medicinal mushrooms that have been reported to possess anti-HIV protease. Experimental procedures We have examined 36 compounds for their potential to be SARS-CoV-2 main protease inhibitors using molecular docking study. Moreover, drug-likeness properties including absorption, distribution, metabolism, excretion and toxicity were evaluated by in silico ADMET analysis. Results Our AutoDock study showed that 25 of 36 candidate compounds have the potential to inhibit the main viral protease based on their binding affinity against the enzyme’s active site when compared to the standard drugs. Interestingly, ADMET analysis and toxicity prediction revealed that 6 out of 25 compounds are the best drug-like property candidates, including colossolactone VIII, colossolactone E, colossolactone G, ergosterol, heliantriol F and velutin. Conclusion Our study highlights the potential of existing mushroom-derived natural compounds for further investigation and possibly can be used to fight against SARS-CoV-2 infection. Taxonomy (classification by evise) Disease, Infectious Disease, Respiratory System Disease, Covid-19, Traditional Medicine, Traditional Herbal Medicine, Phamaceutical Analysis

Neuroprotective Effects against Glutamate-Induced HT-22 Hippocampal Cell Damage and Caenorhabditis elegans Lifespan/Healthspan Enhancing Activity of Auricularia polytricha Mushroom Extracts.

Oxidative stress is associated with several diseases, particularly neurodegenerative diseases, commonly found in the elderly. The attenuation of oxidative status is one of the alternatives for neuroprotection and anti-aging. Auricularia polytricha (AP), an edible mushroom, contains many therapeutic properties, including antioxidant properties. Herein, we report the effects of AP extracts on antioxidant, neuroprotective, and anti-aging activities. The neuroprotective effect of AP extracts against glutamate-induced HT-22 neuronal damage was determined by evaluating the cytotoxicity, intracellular reactive oxygen species (ROS) accumulation, and expression of antioxidant enzyme genes. Lifespan and healthspan assays were performed to examine the effects of AP extracts from Caenorhabditis elegans. We found that ethanolic extract (APE) attenuated glutamate-induced HT-22 cytotoxicity and increased the expression of antioxidant enzyme genes. Moreover, APE promoted in the longevity and health of the C. elegans. Chemical analysis of the extracts revealed that APE contains the highest quantity of flavonoids and a reasonable percentage of phenols. The lipophilic compounds in APE were identified by gas chromatography/mass spectrometry (GC/MS), revealing that APE mainly contains linoleic acid. Interestingly, linoleic acid suppressed neuronal toxicity and ROS accumulation from glutamate induction. These results indicate that AP could be an exciting natural source that may potentially serves as neuroprotective and anti-aging agents

Antidandruff potential of Kaempheria galanga ethanolic extracts for hair cream formulation

The evaluation of Kaempferia galanga, Citrus hystrix and Cinnamomum zeylanicum ethanolic extracts on antifungal activities and zone of inhibition were conducted. The yield for K. galanga, C. hystrix and C. zeylanicum were 0.4, 0.7 and 0.43% of raw dried samples respectively. All the extracts demonstrated 5 mg/mL MIC with C. zeylanicum, K. galanga and C. hystrix average holozones diameter of 14.5 ± 3.8, 12.0 ± 1.8 and 12.0 ± 0.8 mm after 3 days of incubation respectively with no effect on negative control. On the other hand, Zinc Pyrithione being more potent than imidazaole as a positive control with inhibition of 32.8 ± 2.2 and 21.8 ± 3.4 respectively. Based on the findings, the anti-fungal hair cream containing K. galanga ethanolic extract was formulated into oil-in-water cream and the physicochemical properties were evaluated. The cream demonstrated desirable characteristic with no separation between oil and water after vigorously shaken at 14,600 rpm for half an hour. Furthermore the viscosity and pH were 543.7 ± 19.2 and 5.46 ± 0.01 respectively. In conclusion, K galanga ethanolic extract has a potential to be used as an anti-fungal oil in water cream formulation

Simple ammonium salts acting on sigma-1 receptors yield potential treatments for cancer and depression

Sigma-1 and sigma-2 receptors are emerging therapeutic targets. We have identified that simple ammonium salts bind to these receptors and are effective in vivo. Radioligand binding assays were used to obtain structure-activity relationships of these salts. MTS assays were performed to determine their effect on growth in MCF7 and MDA-MB-486 cells. Anticancer properties were tested in NMRI mice transplanted with a fragment of mouse adenocarcinoma (MAC13). Antidepressant activity was tested using the forced-swim test and tailsuspension tests. Dipentylammonium (Ki 43 nM),tripentylammonium (Ki 15 nM) and trihexylammonium (Ki 9 nM) showed high affinity for the sigma-1receptor. Dioctanoylammonium had the highest affinity (K50 0.05 nM); this also showed the highest affinity for sigma-2 receptors (Ki 13 nM). Dipentylammonium was found to have antidepressant activity in vivo. Branched-chain ammonium salts showed lower affinity. Bis(2-ethylhexyl)ammonium (K50 29 μM), triisopentylammonium (K50 196 μM) and dioctanoylammonium showed a low Hill slope,and fitted a 2-site binding model for the sigma-1 receptor. We propose this two-site binding can be used to biochemically define a sigma-1 receptor antagonist. Bis(2-ethylhexyl)ammonium and triisopentylammonium were able to inhibit the growth of tumours in vivo. Cheap, simple ammonium salts act as sigma-1 receptor agonists and antagonists in vivo and require further investigation