CETYL ALCOHOL AND OLEIC ACID SOPHOROLIPIDS EXHIBIT ANTICANCER ACTIVITY

Objective: Sophorolipids (SLs) are glycolipid biosurfactants that have been shown to have anticancer activity. We investigated the anti-cancer activity of cetyl alcohol sophorolipids (CAS) and oleic acid sophorolipids (OAS) in breast cancer (MCF-7, MDA-MB-231), cervical cancer (SiHa, HeLa) and non-cancerous (HaCaT and RAW264.7) cell lines.Methods: For cell viability assay, MCF-7, MDA-MB-231, SiHa, HeLa, HaCaT and RAW264.7 cell lines were treated with different concentrations (0-160 µg/ml) of OAS and CAS for 24h. The cell viability was determined by MTT dye uptake method. Cell proliferation assay was determined by using trypan blue dye exclusion method.Results: Our preliminary data shows that compared to OAS, CAS exhibited more significant reduction in the viability of MCF-7, MDA-MB-231 and SiHa. However, compared to CAS, OAS induced more decrease in viability in HeLa cells. Interestingly, both the types of SLs did not affect the viability of non-cancerous cells. Moreover, CAS, when used as a coating material, induced proliferation in macrophage cell line, RAW264.7.Conclusion: The present study provides an important clue towards the anti-cancer potential of OAS and CAS derived from Candida bombicola. Interestingly, the ability of CAS to promote the proliferation of non-cancerous cells suggests its future application as a scaffold for enhancing the adhesion and proliferation of normal cells.Keywords: Oleic acid sophorolipids, Cetyl alcohol sophorolipids, Breast cancer, Cervical cance

Alpha-linolenic acid regulates the growth of breast and cervical cancer cell lines through regulation of NO release and induction of lipid peroxidation

In the present work, we have analyzed the effect of the essential fatty acid, alpha linolenic acid (ALA) on nitric oxide release as well as induction of lipid peroxidation in breast (MCF-7 and MDA-MB-231) and cervical (SiHa and HeLa) cancer cell lines. ALA-treated cells showed a dose-dependent decrease in cell viability in both breast and cervical cancer cell lines without affecting the viability of non-cancerous transformed HEK 293 cells. Both types of cancer cells treated with ALA demonstrated a significant reduction in nitric oxide (NO) release with a simultaneous increase in lipid peroxidation (LPO). This was followed by a decrease in the mitochondrial membrane potential as well as activation of caspase 3 leading to apoptosis. Thus, ALA regulated the growth of cancer cell lines through induction of lipid peroxidation and modulation of nitric oxide release resulting in apoptosis

COMPARATIVE ANALYSIS OF ANTI-INFLAMMATORY ACTIVITY OF AQUEOUS AND METHANOLIC EXTRACTS OF C. CASSIA AND C. ZEYLANICUM IN RAW264.7, SW1353 AND PRIMARY CHONDROCYTES

Objectives: The objective of this research was to compare the anti-inflammatory activity of aqueous and methanolic extracts of C. cassia (CC) and C. zeylanicum (CZ) in mouse macrophage (RAW264.7) and human chondrosarcoma (SW1353) cell lines as well as in human primary chondrocytes, to correlate their efficacy in management of osteoarthritis (OA) related pathophysiology.Methods: RAW264.7, SW1353 and human primary chondrocytes were pre-treated with aqueous extracts of C. cassia (CCW) and C. zeylanicum (CZW) and methanolic extracts of C. cassia (CCM) and C. zeylanicum (CZM) at various concentrations (0.1-100 µg/ml) for 1 h, followed by stimulation with LPS and IL-1β, respectively. The effect of CCM, CCW, CZM and CZW on the production of nitric oxide (NO) was evaluated by Griess reaction. Evaluation of prostaglandin E2 (PGE2) and leukotriene (LTB4) proteins was performed by EIA-Monoclonal based kits. The effect of these extracts on matrix metalloproteinase (MMPs-2, 9 and 13) levels was analyzed by SensoLyte® fluorimetric MMP assay kit.Results: The methanolic extracts (CCM, CZM) of both the varieties of cinnamon were found to be more effective than the aqueous extracts in terms of PGE2, LTB4 and MMP inhibition.We found that in RAW 264.7, CCM and CZM decreased NO and PGE2 production by45.40%±8.6; 65.63%±5.7 and 79.88%±1.2; 95.91%±0.3, respectively. Similarly, in SW1353 and chondrocytes, CCM decreased PGE2 production by 68.8%±6.4;36.1%±9.5, respectively whereas CZM reduced PGE2 production by 70.2%±2.3; 52.3%±5.4, respectively. Moreover, in SW1353 and chondrocytes CCM decreased LTB4 production by 85.47%±3.03; 99.6%±0.2, respectively whereas CZM reduced LTB4 production by 67.5%±5.6; 75.6%±1.2, respectively. In chondrocytes both CCM and CZM significantly reduced the levels of MMP-2(55.7%±5.2; 73.1%±7.1), MMP-9 (57.5%±4.7; 74.5%±5.2) and MMP-13 (90.1%±2.6; 71.2%±12.5), respectively. However, on comparing the two species of cinnamon, C. zeylanicumwas found to be more effective than C. cassia andthus could be considered for its potential therapeutic application in the management of inflammatory conditions associated with OA.Conclusion: The present study would help in choosing better of the two species of cinnamon for their possible therapeutic application in the management of inflammatory condition associated with OA.Â

EVALUATION OF ACUTE AND SUB-ACUTE TOXICITY OF A STANDARDIZED POLYHERBAL FORMULATION (HC9): AN IN VIVO STUDY

Objective: In the present study, we have performed the acute and sub-acute toxicity of a standardized polyherbal formulation (HC9) in Swiss albino mice. Methods: In acute toxicity study, the mice were orally administered with different doses (1750 and 2000 mg/kg) of HC9 and monitored for 14 d. In the sub-acute toxicity study, animals received HC9 extract by oral gavage at the doses of 250, 500 and 1000 mg/kg/day (????=5/group/sex) for 28 d. At the end of the study, the animals were sacrificed and evaluated for effect of HC9 on biochemical, hematological and histopathological parameters. Results: HC9 did not produce any adverse effects in biochemical, hematological, urine and histopathological parameters in mice. HC9 did not induce any adverse effects in terms of mortality and clinical signs in the acute toxicity study. It was well-tolerated by mice up to 2000 mg/kg/body weight. In sub-acute toxicity study, no treatment-related adverse effects were found in the mice upto 1000 mg/kg/day dose. No significant changes were observed in biochemical and hematological parameters as well as histopathology of tissues (liver, kidney, spleen, heart, lung, thymus, adrenal gland, epididymis and testis/ovary) among mice of either sex. Conclusion: Our results showed that HC9 did not induce any acute and sub-acute toxicity in male and female mice, thereby, suggesting its safety for future clinical application

Protective effects of fecal microbiota transplantation against ischemic stroke and other neurological disorders: an update

The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-β accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer’s disease. In Parkinson’s disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature

Protective effects of fecal microbiota transplantation against ischemic stroke and other neurological disorders: an update

The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-β accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer’s disease. In Parkinson’s disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature

Aqueous Cinnamon Extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential

<p>Abstract</p> <p>Background</p> <p>Chemoprevention, which includes the use of synthetic or natural agents (alone or in combination) to block the development of cancer in human beings, is an extremely promising strategy for cancer prevention. Cinnamon is one of the most widely used herbal medicines with diverse biological activities including anti-tumor activity. In the present study, we have reported the anti-neoplastic activity of cinnamon in cervical cancer cell line, SiHa.</p> <p>Methods</p> <p>The aqueous cinnamon extract (ACE-<it>c</it>) was analyzed for its cinnamaldehyde content by HPTLC analysis. The polyphenol content of ACE-<it>c </it>was measured by Folin-Ciocalteau method. Cytotoxicity analysis was performed by MTT assay. We studied the effect of cinnamon on growth kinetics by performing growth curve, colony formation and soft agar assays. The cells treated with ACE-<it>c </it>were analyzed for wound healing assay as well as for matrix metalloproteinase-2 (MMP-2) expression at mRNA and protein level by RT-PCR and zymography, respectively. Her-2 protein expression was analyzed in the control and ACE-<it>c </it>treated samples by immunoblotting as well as confocal microscopy. Apoptosis studies and calcium signaling assays were analyzed by FACS. Loss of mitochondrial membrane potential (Δψ_m) in cinnamon treated cells was studied by JC-1 staining and analyzed by confocal microscopy as well as FACS.</p> <p>Results</p> <p>Cinnamon alters the growth kinetics of SiHa cells in a dose-dependent manner. Cells treated with ACE-<it>c </it>exhibited reduced number of colonies compared to the control cells. The treated cells exhibited reduced migration potential that could be explained due to downregulation of MMP-2 expression. Interestingly, the expression of Her-2 oncoprotein was significantly reduced in the presence of ACE-<it>c</it>. Cinnamon extract induced apoptosis in the cervical cancer cells through increase in intracellular calcium signaling as well as loss of mitochondrial membrane potential.</p> <p>Conclusion</p> <p>Cinnamon could be used as a potent chemopreventive drug in cervical cancer.</p

Synthesis and characterization of gold nanoparticles using Ficus religiosa extract

We report a cost effective and eco-friendly biosynthesis of gold nanoparticles (F-AuNPs) using aqueous extract of Ficus religiosa as the reducing and stabilizing agent. These nanoparticles were characterized by various techniques such as UV-Vis, XRD, TEM and FTIR. The characteristic surface plasmon peak was observed at 540 nm while XRD analysis suggested it to be a face-centered cubic (fcc) structure with peaks at 38.06, 44.46, 64.75 and 77.56. FTIR studies indicated the capping of the nanoparticles with polyphenols, amines and carboxylates present in the extract of Ficus religiosa whereas TEM analysis showed spherical morphology with other shapes such as triangles and hexagons. The F-AuNPs were found to be non-toxic to HEK 293 cells, thereby suggesting their potential application in the field of nanobiotechnology

SMAR1 and Cux/CDP modulate chromatin and act as negative regulators of the TCRβ enhancer (Eβ)

Chromatin modulation at various cis-acting elements is critical for V(D)J recombination during T and B cell development. MARβ, a matrix-associated region (MAR) located upstream of the T cell receptor β (TCRβ) enhancer (Eβ), serves a crucial role in silencing Eβ-mediated TCR activation. By DNaseI hypersensitivity assays, we show here that overexpression of the MAR binding proteins SMAR1 and Cux/CDP modulate the chromatin structure at MARβ. We further demonstrate that the silencer function of MARβ is mediated independently by SMAR1 and Cux/CDP as judged by their ability to repress Eβ-dependent reporter gene expression. Moreover, the repressor activity of SMAR1 is strongly enhanced in the presence of Cux/CDP. These two proteins physically interact with each other and colocalize within the perinuclear region through a SMAR1 domain required for repression. The repression domain of SMAR1 is separate from the MARβ binding domain and contains a nuclear localization signal and an arginine–serine (RS)-rich domain, characteristic of pre-mRNA splicing regulators. Our data suggest that at the double positive stage of T cell development, cis-acting MARβ elements recruit the strong negative regulators Cux and SMAR1 to control Eβ-mediated recombination and transcription

Cinnamaldehyde, cinnamic acid, and cinnamyl alcohol, the bioactives of cinnamomum cassia exhibit HDAC8 inhibitory activity : an in vitro and in silico study

BACKGROUND : The altered expression of histone deacetylase family member 8 (HDAC8) has been found to be linked with various cancers, thereby making its selective inhibition a potential strategy in cancer therapy. Recently, plant secondary metabolites, particularly phenolic compounds, have been shown to possess HDAC inhibitory activity. OBJECTIVE : In the present work, we have evaluated the ability of cinnamaldehyde (CAL), cinnamic acid (CA), and cinnamyl alcohol (CALC) (bioactives of Cinnamomum) as well as aqueous cinnamon extract (ACE), to inhibit HDAC8 activity in vitro and in silico. MATERIALS AND METHODS : HDAC8 inhibitory activity of ACE and cinnamon bioactives was determined in vitro using HDAC8 inhibitor screening kit. Trichostatin A (TSA), a well‑known anti‑cancer agent and HDAC inhibitor, was used as a positive control. In silico studies included molecular descriptor Analysis molecular docking absorption, distribution, metabolism, excretion, and toxicity prediction, density function theory calculation and synthetic accessibility program. RESULTS : Pharmacoinformatics studies implicated that ACE and its Bioactives (CAL, CA, and CALC) exhibited comparable activity with that of TSA. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals along with binding energy of cinnamon bioactives were comparable with that of TSA. Molecular docking results suggested that all the ligands maintained two hydrogen bond interactions within the active site of HDAC8. Finally, the synthetic accessibility values showed that cinnamon bioactives were easy to synthesize compared to TSA. CONCLUSION : It was evident from both the experimental and computational data that cinnamon bioactives exhibited significant HDAC8 inhibitory activity, thereby suggesting their potential therapeutic implications against cancer.MA Islam was funded by the University of Pretoria Vice Chancellor’s post doctoral and NRF Innovation Post-doctoral fellowship schemes, South Africa, and Choudhari was funded by CSIR Senior Research Fellowship.http://www.phcog.comam2018Chemical Patholog