Diallyl Trisulfide Research Articles

Hypothermia-Triggered Mesoporous Silica Particles for Controlled Release of Hydrogen Sulfide to Reduce the I/R Injury of the Myocardium.

Despite the fact that heart transplantation (HTx) is a relatively mature procedure, heart ischemic and reperfusion (I/R) injury during HTx remains a challenge. Even after a successful operation, the heart will be at risk of primary graft failure and mortality during the first year. In this study, temperature-sensitive polymer poly(N-n-propylacrylamide-co-N-tert-butyl acrylamide) (PNNTBA) was coated on diallyl trisulfide (DATS)-loaded mesoporous silica nanoparticles (DATS-MSN) to synthesize hypothermia-triggered hydrogen sulfide (H2S) releasing particles (HT-MSN). Because the PNNTBA shell dissolves in phosphate-buffered saline at 4 °C, the loaded DATS could continuously release H2S within 6 h when activated by glutathione (GSH). Furthermore, after co-culturing biocompatible HT-MSN with cardiomyocytes, H2S released from HT-MSN at 4 °C was found to protect cardiomyocytes from ischemic and reperfusion (I/R) injury. In detail, the rate of cell apoptosis and lactate dehydrogenase activity was decreased, as manifested by increased BCL-2 expression and decreased BAX expression. More importantly, in an isolated heart preservation experiment, HT-MSN demonstrated potent protection against cardiac I/R injury and reduced expression of inflammatory factors TNF-α and IL-1β. This study provided a new method for the controlled release of H2S by the donor and myocardial protection from I/R injury.

Metal-doped 2D rGO nano-sheets fabrication utilizing plant source bio-molecules and application in the epoxy anti-corrosive coating: Combined experimental and DFT-D modeling investigations

Recently, graphene-filled polymeric composites have been utilized for achieving durable active corrosion protection properties in seawater solutions. The utilization of reduced graphene oxide (rGO) is highly recommended for this purpose. Although the traditional reductants can successfully reduce the GO layers, employing green active agents is far more affordable. In the present study, Mustard seed extract was introduced as a novel cost-effective, and green reductant for GO layers since it includes active agents like arabinose, allyl isothiocyanate, galactose, xylose, diallyl trisulfide, and rhamnose molecules. For boosting the active protection property, the rGO nano-sheets were doped with Zn (II) ions (Zn@rGO) as the inorganic inhibitor. The synthesized nanosheets' anti-corrosion impacts in the solution phase were illustrated by polarization and EIS techniques. The obtained results have proved that the Zn@rGO containing saline solution exposed steel samples resulted in 88% degree of inhibition in mixed mode. The EIS assessments carried out over the scratched epoxy composite reflected that the coating resistance was raised from 12,491 Ω cm2 to 47,480 Ω cm2, affirming the inhibitive corrosion prevention potency of the Zn@rGO/EP composite. The FE-SEM captures have displayed that the inhibitive layer filled the scratched zones successfully. Besides, the intact coating's high resistance (over 30 GΩ.cm2) indicated that the constructed nano-filler could effectively promote the EP coating barrier index. The optical captures after conducting a salt-spray test have demonstrated that after the EP anti-corrosion performance was significantly improved in the presence of Zn@rGO nano-layers. The coating delamination diameter reduction from 28 mm for the neat epoxy to 11 mm for the Zn@rGO loaded coating was recorded in the cathodic disbondment test. In addition, the theoretical findings ensured the affinity of the zinc ions/ME compounds for adsorption on the GO layers.

Diallyl Trisulfide Promotes Placental Angiogenesis by Regulating Lipid Metabolism and Alleviating Inflammatory Responses in Obese Pregnant Mice.

The placental tissue serves as an exchanger between the mother and the fetus during pregnancy in mammals. Proper placental angiogenesis is central to the health of both the mother and the growth and development of the fetus. Maternal obesity is associated with impaired placental function, resulting in restricted placental blood vessel development and fetal developmental disorders. Hydrogen sulfide (H2S) is a ubiquitous second messenger in cells that has many biological effects such as promoting angiogenesis, anti-inflammation, anti-oxidation and promoting lipid metabolism. However, in the case of maternal obesity, whether H2S can be used as an important signaling molecule to regulate body metabolism, alleviate placental inflammation levels and promote placental angiogenesis is still unclear. In this study, diallyl trisulfide (DATS), which is a well-known H2S donor, was derived from garlic and used to treat obese pregnant mice induced by a high-fat diet, to determine its effects on lipid metabolism and inflammation, as well as placental morphology and placental angiogenesis. Here, we show that DATS treatment increased litter size and alive litter size. DATS improved the H2S level in the serum and placenta of the mice. In addition, DATS treatment improved insulin resistance and lipid metabolism, reduced the inflammatory response and alleviated placental vascular dysplasia caused by obesity in obese mice. In summary, our research revealed that H2S is an important signaling molecule in vivo, which can regulate placental angiogenesis and improve the reproductive performance in maternal obesity. The addition of H2S donor DATS during pregnancy promoted placental angiogenesis by regulating lipid metabolism and alleviating inflammatory responses in obese pregnant mice.

Endogenous and exogenous hydrogen sulfide modulates urothelial bladder carcinoma development in human cell lines

The role of H2S in urothelial carcinoma (UC) is still unclear. Here we have evaluated the expression of H2S producing enzymes as well as the effect of endogenous and exogenous H2S on human bladder UC cells. In human UC cells the expression of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST); is significantly lower as compared to healthy cells. A modulatory role for the H2S pathway is supported by the finding that, the overexpression of CSE or CBS, but not 3-MST, inhibits cell proliferation and promotes apoptosis. A similar effect is obtained by using exogenous H2S. Diallyl trisulfide (DATS), which is a fully characterized H2S donor, inhibits the proliferation of UC cells in a time and concentration-dependent manner as well as promotes apoptosis. Moreover, DATS also induces autophagy, as determined by transcriptomic and western blot analysis. Finally, DATS inhibits mRNA expression levels of canonical markers of epithelial-mesenchymal transition by limiting migration and clonogenic ability of human UC cells in vitro. In conclusion, in urothelial carcinoma, there is an impairment of H2S pathway that involves CSE and CBS- derived hydrogen sulfide. Thus, targeting H2S signaling pathway in urothelial carcinoma could represent a novel therapeutic strategy.

Phytochemicals in the Management of Arsenic Toxicity.

Arsenic toxicity is a major concern due to its deleterious consequences for human health. Rapid industrialization also has weakened the quality of the environment by introducing pollutants that may disrupt balanced ecosystems, adversely and irreversibly impacting humans, plants, and animals. Arsenic, an important toxicant among all environmental hazards, can lead to several detrimental effects on cells and organs, impacting the overall quality of life. Nevertheless, arsenic also has a rich history as a chemotherapeutic agent used in ancient days for the treatment of diseases such as malaria, cancer, plague, and syphilis when other chemotherapeutic agents were yet to be discovered. Arsenicosis-mediated disorders remain a serious problem due to the lack of effective therapeutic options. Initially, chelation therapy was used to metabolically eliminate arsenic by forming a complex, but adverse effects limited their pharmacological use. More recently, plant-based products have been found to provide significant relief from the toxic effects of arsenic poisoning. They act by different mechanisms affecting various cellular processes. Phytoconstituents such as curcumin, quercetin, diallyl trisulfide, thymoquinone, and others act via various molecular pathways, primarily by attenuating oxidative damage, membrane damage, DNA damage, and proteinopathies. Nonetheless, most of the phytochemicals reviewed here protect against the adverse effects of metal or metalloid exposure, supporting their consideration as alternatives to chelation therapy. These agents, if used prophylactically and in conjunction with other chemotherapeutic agents, may provide an effective approach for management of arsenic toxicity. In a few instances, such strategies like coadministration of phytochemicals with a known chelating agent have led to more pronounced elimination of arsenic from the body with lesser off-site adverse effects. This is possible because combination treatment ensures the use of a reduced dose of chelating agent with a phytochemical without compromising treatment. Thus, these therapies are more practical than conventional therapeutic agents in ameliorating arsenic-mediated toxicity. This review summarizes the potential of phytochemicals in alleviating arsenic toxicity on the basis of available experimental and clinical evidence.

Diallyl trisulfide plays an antifibrotic role by inhibiting the expression of Bcl-2 in hepatic stellate cells.

Hepatic fibrosis is an important early stage in the evolution of liver cirrhosis, and specific medicine and therapeutic measures are unavailable to date. Hepatic stellate cells (HSCs) are the main cells involved in the formation of hepatic fibrosis, and induction of the apoptosis of HSCs is an important strategy for the treatment of hepatic fibrosis. Diallyl trisulfide (DATS) is a natural product and is the main active ingredient in garlic. However, the exact molecular mechanisms underlying HSC apoptosis induced by DATS are not well understood. This study aimed to analyze the efficiency and mechanism of DATS in hepatic fibrosis. Different concentrations (25, 50, 100, and 200 μM) of DATS were used to treat HSCs. Changes in cell morphology and formation of apoptotic bodies were observed under an inverted microscope and an electric microscope. Bcl‐2 signaling involving Bax, Caspase‐3, Caspase‐6, Caspase‐8, Caspase‐9, p53, Apaf‐1, and Cyto‐c in fibrosis were examined, which is a critical step in the evaluation of antihepatic fibrosis agents. We also evaluated the effect of DATS on the cellular morphology of HSCs and apoptosis‐related factors under different Bcl‐2 expression states. Our results suggest that DATS regulates hepatic fibrosis by blocking the Bcl‐2 signaling pathway and upregulating the Bax/Bcl‐2 ratio.

Monocarboxylate transporter 1 is a novel target for breast cancer stem like-cell inhibition by diallyl trisulfide.

Diallyl trisulfide (DATS) is a promising small molecule phytochemical that exhibits in vitro and in vivo activity in multiple preclinical solid tumor models including breast cancer, but the underlying mechanism is not fully understood. We have shown previously that forkhead box Q1 (FoxQ1) transcription factor is a novel target for breast cancer stem-like cells (bCSC) inhibition by DATS. Analysis of the breast TCGA (The Cancer Genome Atlas) data revealed that FoxQ1 expression was positively associated with that of SLC16A1/monocarboxylate transporter 1 (MCT1). Western blot analysis confirmed increased expression of MCT1 protein in SUM159 (basal-like) and MCF-7 cells (luminal-type) stably transfected to overexpress FoxQ1. Furthermore, FoxQ1 was recruited to the promoter of SLC16A1/MCT1. Treatment of SUM159 and MCF-7 cell lines with DATS resulted in suppression of MCT1 protein level that was accompanied by a decrease in intracellular and secreted levels of lactate. Overexpression or knockdown of MCT1 protein failed to alter DATS-mediated inhibition of colony formation or cell migration when compared to corresponding control cells. On the other hand, overexpression of MCT1 protein conferred partial but statistically significant protection against DATS-mediated inhibition of bCSC fraction (CD49fhigh /CD44high and aldehyde dehydrogenase 1 activity). The size of the mammospheres was relatively smaller in the DATS-treated group compared to control group. Inhibition of bCSC upon DATS treatment was augmented by knockdown of the MCT1 protein. In conclusion, the present study reveals that MCT1 is a novel target for bCSC inhibition by DATS treatment.

Effects of Diallyl Trisulfide on TNF‐α‐stimulated Genetically different Triple‐Negative Breast Cancer Cells

Many studies have demonstrated the potential anticancer properties of garlic and their respective constituents through in vitro and in vivo studies. Diallyl trisulfide (DATS), an organosulfur compound of garlic, has been shown to prevent and inhibit breast carcinogenesis through various signaling pathways. The triple‐negative breast cancer (TNBC) subtype, which accounts for approximately 15% of all breast cancers, usually behaves more aggressively than other types of breast cancer and is more challenging to treat. Cancer progression is associated with the overexpression of the monocyte chemotactic protein‐1 (MCP‐1. MCP‐1, also known as C‐C motif chemokine ligand‐2 (CCL2), plays a significant role in breast cancer cell signaling, leading to increased cell proliferation, immune suppression, epithelial‐to‐mesenchymal transition (EMT), and angiogenesis. This study explored DATS effects on the genetically different triple‐negative breast cancer cells, MDA‐MB‐231 and MDA‐MB‐468. DATS effects on TNF‐α induced TNBC cells were examined via trypan blue exclusion test, wound‐healing assay, human cytokine arrays, ELISA, and RT‐PCR. The results showed that DATS induced cytotoxicity in a dose and time‐response way in MDA‐MB‐231 and MDA‐MB‐468 cell lines. Wound healing assays demonstrated that DATS significantly inhibited cell migration after a 12 h exposure in both cell lines. Protein expression of CCL2/MCP‐1, IL‐6, PDGF‐BB, NT‐3, and GM‐CSF was increased in the TNF‐α‐treated cells. However, the cotreatment with DATS and TNF‐α showed that the compound significantly decreased the expression of CCL2/MCP‐1 in MDA‐MB‐231 but not in MDA‐MB‐468 cells; data confirmed with ELISA. Moreover, DATS significantly down‐regulated mRNA expression of IKBKE and MAPK8 in both cell lines, indicating a possible effect in genes involved in the NF‐κB and MAPK signaling. The data show that genetically different cells may respond in a different way to DATS treatment. In conclusion, DATS may be a potential candidate for breast cancer therapy to slow TNBC progression.

대체당 알룰로스를 이용한 고추장 양념장의 주요 방향 화합물 특성

Purpose: This study aimed to investigate the flavor characteristics of the Gochujang condiment and its flavor compounds when it was heated with the addition of allulose. Methods: The Gochujang condiment samples were prepared with the addition of 0%, 25%, 50%, 75%, 100% allulose, and sugar for sweetness and heated for 30 minutes. The solid-phase micro-extraction (SPME) method was used to capture the flavor aroma, gas chromatography-mass spectrometry (GC-MS), and gas chromatography-olfactometry (GC-O) were used for the analysis. Results: The volatile flavor components were analyzed to evaluate the flavor characteristics of the processed Gochujang condiment. A total of 43 volatile flavor components were identified with the heat treatment, among which diallyl trisulfide showed the highest peak, and diallyl disulfide, methyl-2-propenyl trisulfide, β-phellandrene, and β-caryophyllene also had high peaks. These five high-peak ingredients play an important role in determining the taste of the Gochujang condiment. It was confirmed that the volatile component was diallyl trisulfide, which increased as the allulose content increased. A total of 16 flavoring active ingredients of the condiment were identified. Also, most sulfur compounds and terpene were identified. Allyl methyl disulfide, dimethyl trisulfide, diallyl disulfide, β-phellandrene, and methyl 2-propenyl trisulfide played an important role in the flavoring of the Gochujang condiment. Conclusion: The main volatile components of the flavor compounds generated by the heat treatment included diallyl trisulfide, diallyl disulfide, methyl-2-propenyl trisulfide, β-phellandrene, and β-caryophyllene with high peak areas. The quantum of diallyl trisulfide increased as the allulose content increased. Allyl methyl disulfide, dimethyl trisulfide, diallyl disulfide, β-phellandrene, and methyl 2-propenyl trisulfide were identified as flavoring active compounds, and each of these contributed to the flavor of the Gochujang condiment.

Garlic essential oil-based nanoemulsion carrier: Release and stability kinetics of volatile components.

An O/W nanoemulsion of garlic essential oil (GEO) at different oil‐to‐emulsion (O/E) ratios (5%, 10%, 15%, and 25%) was formulated to protect the volatile components of GEO. The effects of O/E ratios on the encapsulation efficiency (EE%) of volatile compounds and droplet size of nanoemulsions were studied. The results showed that with increasing in E/O ratio, droplet size increased while EE% decreased so that the droplet size was below 100 nm for all samples and the EE% was almost above 80% for most samples. The effects of various factors such as temperature (5°C–45°C), pH values (3–7), ionic strength (0–500 mM), and O/E ratios (5%–25%) on kinetic of nanoemulsions stability were studied. Reducing pH values and raising the temperature, ionic strength, and O/E ratios intensified the instability process and constant rate of instability in all nanoemulsions. The effects of temperature and O/E ratios on the release kinetics of volatile components were evaluated over time, and kinetic parameters such as release rate constant (k), Q10, and activation energy (Ea) were calculated in which results showed a zero‐degree model to describe the release kinetic behavior of most nanoemulsions. Both temperature and O/E ratios factors as well as their interaction (which had a synergistic effect) had a significant effect on increasing the release rate of volatiles so that the degree of reaction rate was changed from zero to the first order at simultaneous high levels of both factors. FT‐IR spectroscopy was carried out to study interactions among nanoemulsion ingredients. The presence of sulfur‐containing functional groups of garlic oil (thiosulphate, diallyl trisulfide, etc.) in nanoemulsions was confirmed by FT‐IR.

Albumin-assembled copper-bismuth bimetallic sulfide bioactive nanosphere as an amplifier of oxidative stress for enhanced radio-chemodynamic combination therapy.

The tumor microenvironment with overexpressed hydrogen peroxide (H2O2) and reinforced antioxidative system (glutathione, GSH) becomes a double-edged sword for the accessibility of nano-therapy. Since reactive oxygen species (ROS) are easily quenched by the developed antioxidative network, ROS-based treatments such as chemodynamic therapy (CDT) and radiotherapy (RT) for killing cancer cells are severely attenuated. To overcome such limitations, a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin (BSA) based bioactive nanospheres that are BSA assembled with in situ generated copper-bismuth sulfide nanodots and diallyl trisulfide (DATS). The copper-bismuth sulfide nanodots react with H2O2 to produce •OH and release Cu2+. Then, the Cu2+ further depletes GSH to generate Cu+ for more •OH generation in the way of Fenton-like reaction. Such a cascade reaction can initiate •OH generation and GSH consumption to realize CDT. The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells. With the sensitization of increased oxidative stress and high Z element Bi, an enhanced radio-chemodynamic combination therapy is achieved. The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.

Bioresponsive nano-antibacterials for H2S-sensitized hyperthermia and immunomodulation against refractory implant-related infections.

There is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial biofilm infections. Here, a novel “gas-sensitized hyperthermia” strategy is proposed for appreciable bacteria killing by the smart design of a metal-organic framework (MOF)–sealed Prussian blue–based nanocarrier (MSDG). Once the biofilm microenvironment (BME) is reached, the acidity-activated MOF degradation allows the release of diallyl trisulfide and subsequent glutathione-responsive generation of hydrogen sulfide (H2S) gas. Upon near-infrared irradiation, H2S-sensitized hyperthermia arising from MSDG can efficiently eliminate biofilms through H2S-induced extracellular DNA damage and heat-induced bacterial death. The generated H2S in the biofilm can stimulate the polarization of macrophages toward M2 phenotype for reshaping immune microenvironment. Subsequently, the secretion of abundant regeneration-related cytokines from M2 macrophages accelerates tissue regeneration by reversing the infection-induced pro-inflammatory environment in an implant-related infection model. Collectively, such BME-responsive nano-antibacterials can achieve biofilm-specific H2S-sensitized thermal eradiation and immunomodulatory tissue remodeling, thus realizing the renaissance of precision treatment of refractory implant–related infections.

Garlic (Allium sativum L.): Its Chemistry, Nutritional Composition, Toxicity, and Anticancer Properties.

The current review discuss the chemistry, nutritional composition, toxicity, and biological functions of garlic and its bioactive compounds against various types of cancers via different anticancer mechanisms. Several scientific documents were found in reliable literature and searched in databases viz Science Direct, PubMed, Web of Science, Scopus, and Research Gate were carried out using keywords such as "garlic", "garlic bioactive compounds", "anticancer mechanisms of garlic", "nutritional composition of garlic", and others. Garlic contains several phytoconstituents with activities against cancer, and compounds such as diallyl trisulfide (DATS), allicin, and diallyl disulfide (DADS), diallyl sulfide (DAS), and allyl mercaptan (AM). The influence of numerous garlic- derived products, phytochemicals, and nanoformulations on the liver, oral, prostate, breast, gastric, colorectal, skin, and pancreatic cancers has been studied. Based on our search, the bioactive molecules in garlic were found to inhibit the various phases of cancer. Moreover, the compounds in this plant also abrogate the peroxidation of lipids, activity of nitric oxide synthase, epidermal growth factor (EGF) receptor, nuclear factor-kappa B (NF-κB), protein kinase C, and regulate cell cycle and survival signaling cascades. Hence, garlic and its bioactive molecules exhibit the aforementioned mechanistic actions, and thus, they could be used to inhibit the induction, development, and progression of cancer. The review describes the nutritional composition of garlic, its bioactive molecules, and nanoformulations against various types of cancers, as well as the potential for developing these agents as antitumor drugs.

Diallyl Trisulfide Induces Apoptosis in Breast Ductal Carcinoma In Situ Derived and Minimally Invasive Breast Cancer Cells.

Breast ductal carcinoma in situ (DCIS) is a localized form of breast cancer that can progress to invasive breast cancer. Diallyl trisulfide (DATS) is a bioactive compound from Allium vegetables reported to induce anticancer effects in several cancer models. The objective of this study was to characterize DATS-induced apoptosis in breast DCIS and minimally invasive breast cancer cells. Breast DCIS cells SUM 102PT (ductal carcinoma in situ with areas of micro-invasion) and SUM 225CWN (chest wall recurrence of ductal carcinoma in situ) were used in this study. DATS induced a dose-dependent reduction in the colony formation ability of breast DCIS cells. DATS inhibited DCIS cell growth by inducing apoptosis as shown by a dose-dependent increase in cytoplasmic histone-associated DNA fragmentation. Induction of apoptosis was more pronounced in SUM 102PT cells than in SUM 225CWN cells at similar concentrations of DATS. DATS-induced apoptosis was characterized by a dose-dependent increase in cleaved poly-ADP ribose polymerase (PARP). DATS treatment resulted in an increase in the cytochrome c levels and cleavage of caspases 3, 7, and 9. This study shows that DATS inhibits cell proliferation and induces apoptosis in breast DCIS derived and minimally invasive breast cancer cells, and supports further investigation of DATS as a potential chemopreventive agent for DCIS.

Gene Expression Changes by Diallyl Trisulfide Administration in Chemically-induced Mammary Tumors in Rats.

Diallyl trisulfide (DATS) was shown to be a potent inhibitor of luminal-type MCF-7 xenograft growth in vivo. The present study was conducted to determine the preventive effect of DATS administration using an N-methyl-N-nitrosourea (MNU)-induced rat mammary tumor model, which shares molecular resemblance to luminal-type human breast cancers. The DATS administration (50 mg/kg body weight, 5 times/week) was safe, but did not reduce mammary tumor latency, incidence, burden or multiplicity. Therefore, we conducted RNA-seq analysis using mammary tumors from control and DATS-treated rats (n = 3 for each group) to gain insights into lack of mammary tumor prevention by this phytochemical. The gene ontology and the Kyoto encyclopedia of genes and genomes pathway analyses of the RNA-seq data revealed upregulation of genes associated with ribosomes, translation, peptide biosynthetic/metabolic process, and oxidative phosphorylation but downregulation of genes associated with mitogen-activated protein kinases. A total of 33 genes associated with ribosomes were significantly upregulated by DATS treatment, including RPL11 and RPS14. Western blotting confirmed upregulation of RPL11 and neurofascin protein expression in mammary tumors from DATS-treated rats when compared to controls. A statistically significant increase in protein level of c-Jun N-terminal kinase 2 was also observed in tumors from DATS-treated rats when compared to controls. On the other hand, expression of complex I subunits NDUFV1 or NDUFS1 was not affected by DATS treatment. These results offer potential explanations for ineffectiveness of DATS in the chemically-induced rat mammary tumor model. Inhibitors of the proteins upregulated by DATS may be needed to improve chemopreventive efficacy of this phytochemical.

Lipid-Based Nanoparticle Formulation of Diallyl Trisulfide Chemosensitizes the Growth Inhibitory Activity of Doxorubicin in Colorectal Cancer Model: A Novel In Vitro, In Vivo and In Silico Analysis.

Garlic’s main bioactive organosulfur component, diallyl trisulfide (DATS), has been widely investigated in cancer models. However, DATS is not suitable for clinical use due to its low solubility. The current study seeks to improve DATS bioavailability and assess its chemopreventive and chemosensitizing properties in an AOM-induced colorectal cancer model. The polyethylene glycol coated Distearoylphosphatidylcholine/Cholesterol (DSPC/Chol) comprising DATS-loaded DATSL and doxorubicin (DOXO)-encapsulated DOXL liposomes was prepared and characterized. The changes in the sensitivity of DATS and DOXO by DATSL and DOXL were evaluated in RKO and HT-29 colon cancer cells. The synergistic effect of DATSL and DOXL was studied by cell proliferation assay in the combinations of IC10, IC25, and IC35 of DATSL with the IC10 of DOXL. AOM, DATSL, and DOXL were administered to different groups of mice for a period of 21 weeks. The data exhibited ~93% and ~46% entrapment efficiency of DATSL and DOXL, respectively. The size of sham liposomes was 110.5 nm, whereas DATSL and DOXL were 135.5 nm and 169 nm, respectively. DATSL and DOXL exhibited significant sensitivity in the cell proliferation experiment, lowering their IC50 doses by more than 8- and 14-fold, respectively. However, the DATSL IC10, IC25, and IC35 showed escalating chemosensitivity, and treated the cells in combination with DOXL IC10. Analysis of histopathological, cancer marker enzymes, and antioxidant enzymes revealed that the high dose of DATSL pretreatment and DOXL chemotherapy is highly effective in inhibiting AOM-induced colon cancer promotion. The combination of DATSL and DOXL indicated promise as a colorectal cancer treatment in this study. Intermolecular interactions of DATS and DOXO against numerous cancer targets by molecular docking indicated MMP-9 as the most favourable target for DATS exhibiting binding energy of −4.6 kcal/mol. So far, this is the first research to demonstrate the chemopreventive as well as chemosensitizing potential of DATSL in an animal model of colorectal cancer.

Antifungal activity, antibiofilm and synergic effect of diallyl disulfide and diallyl trisulfide against Candida albicans

The objective of the present study was to determine the antifungal activity, antibiofilm and synergic effect of the compounds diallyl disulfide and diallyl trisulfide in combination with antifungal agents against clinical isolates of Candida albicans, including also a computational study. Antimicrobial sensitivity tests were performed using the broth microdilution method to determine the minimum inhibitory concentration against C. albicans strains and modulatory activity using the checkerboard technique. The biofilm formation was evaluated by biomass quantification using the violet crystal staining method. For the study of molecular docking computer simulations. The constituents showed relevant antifungal activity against strains of C. albicans. In the modulatory activity assay, demonstrated a synergistic interaction with fluconazole and amphotericin B, with an increase in its antifungal action. The diallyl disulfide, diallyl trisulfide and fluconazole ligands formed complexes with ALS3 enzyme. Then, both compounds were considered promising products for the development of new drugs to prevent candidiasis.

An NIR photothermal-responsive hybrid hydrogel for enhanced wound healing

Moderately regulating vascularization and immune microenvironment of wound site is necessary to achieve scarless wound healing of the skin. Herein, we have prepared an angiogenesis-promoting and scar-preventing band-aid with a core-shell structure, that consists of MXene-loaded nanofibers (MNFs) as the core and dopamine-hyaluronic acid hydrogel (H) as the shell (MNFs@V–H@DA) to encapsulate a growth factor (vascular endothelial growth factor, VEGF, abbreviated as V) and H2S donor (diallyl trisulfide, DATS, abbreviated as DA). The continuous release of DA from this system produced H2S, which would successfully induce macrophages to polarize into M2-lile phenotype, regulating the immune microenvironment and inhibiting an excessive inflammatory response at the wound sites. It is conducive to the proliferation of skin cells, facilitating the wound healing. In addition, an appropriate amount of VEGF can be released from the MXene nanofibrous skeleton by adjusting the time of near-infrared (NIR) light exposure, preventing excessive neovascularization and extracellular matrix deposition at the wound sites. Collectively, this NIR photothermal-responsive band-aid achieved scarless wound healing through gradient-controlled vascularization and a related immune sequential reaction of damaged skin tissue.

One-pot extraction and enrichment of diallyl trisulfide in garlic oil using an eco-friendly solvent-free microwave extraction method

The H2S-releasing donor capabilities of garlic polysulfanes, particularly diallyl trisulfide, have been shown to exhibit cardioprotective, antiatherosclerotic, and anticarcinogenic effects. These properties lead to the ubiquitous use of garlic oil in pharmaceuticals; nevertheless, there is a lack of a simple, optimal, and environmentally friendly approach for increasing diallyl trisulfide levels. This study aimed to establish a one-pot extraction and enrichment method for diallyl trisulfide in garlic oil using solvent-free microwave extraction (SFME). In the SFME processes, a face-centered central composite design (FCCCD) was applied by treating the moisture content, microwave power, and irradiation time as independent factors, whereas the response was volatile oil yield. The extraction method was optimized using response surface methodology and Derringer’s desirability function. Under optimal conditions, SFME was implemented to assure the maximum qualitative and quantitative quality of garlic oils collected from different origins. The volatile oils obtained were analyzed by gas chromatography−mass spectrometry. The optimum conditions for SFME were a 68% moisture content and irradiation at 640 W for 20 min, yielding 0.30 ± 0.02% w/w garlic oil. The proposed SFME conditions were more efficient than hydrodistillation (HD) in production yields and the proportion of diallyl trisulfides. When the proposed conditions were implemented, garlic oil yields varied between 0.14% w/w and 0.32% w/w, with a high proportion of the target diallyl trisulfide. This finding highlights an appropriate model for extracting diallyl trisulfide-rich garlic oil using an eco-friendly technology that is more efficient than the conventional HD method.

In vitro anti-synovial sarcoma effect of diallyl trisulfide and mRNA profiling.

Synovial sarcoma (SS) is a malignant soft tissue sarcoma and its natural history is a long, indolent clinical course followed by high rate of local recurrence and distant metastasis. Current therapies are still limited in increasing satisfactory of 5-year survival, especially for patients with recurrence and metastasis. Accordingly, finding new therapeutic drug for SS treatment is clinically urgent need. Diallyl trisulfide (DATS), a bioactive compound derived from garlic, is reported as a promising anti-cancer agent for various carcinomas. However, its effect on anti-SS remains unknown. This study investigated the anti-SS effect of DATS in human synovial sarcoma SW982 cells. CCK-8 assay were used to examine the cell viability. High-content Imaging System was used to examine the apoptosis, intracellular ROS and autophagy. Flow cytometry was used to detect cell cycle. qPCR and Western blot were used to examine the expression of related mRNA and protein. High-throughput RNA-sequencing and bio-information analysis were used to investigate the mRNA profiling. The results showed a suppressive effect of DATS on tumor biology of SW982 cells including inducing apoptosis, triggering G2/M cell cycle arrest, elevating intracellular ROS and damaging mitochondria. Further high-throughput RNA-sequencing analysis clarified a comprehensive molecular portrait for DATS-induced transcriptional regulation. Besides, protein-protein interaction (PPI) analysis demonstrated that a network consisted of FOXM1, CCNA2, CCNB1, MYBL2, PLK1 and CDK1 might be response for DATS-induced G2/M cell cycle arrest and increased intracellular ROS. Notably, protein feature analysis revealed structure enrichment in microtubule network like kinesin motors domain, and tubulin domain. Molecular function analysis suggested that DATS-induced dysfunction of microtubule network might be the major cause for its effect on cell cycle arrest and successive apoptosis. Furthermore, 28 hub genes (including KIF2C, PLK1, CDK1, BIRC5, CCNB2, CENPF, TPX2, TOP2A and so on) were determined. Finally, pathway analysis showed that DATS-induced differentially expressed genes were mainly involved in cell cycle. Collectively, our findings for the first time provided the DATS-induced cellular response and transcriptional profiling of SW982 cells, which proposes that suppression of DATS on SS is multi-targeted and represent a therapeutic evidence for SS.