[Cloning and functional analysis of AcFMO from onion during alliine biosynthesis].

Flavin-containing monooxygenase (FMO) is the key enzyme in the biosynthesis pathway of CSOs with sulfur oxidation. In order to explore the molecular regulatory mechanism of FMO in the synthesis of onion CSOs, based on transcriptome database and phylogenetic analysis, one AcFMO gene that may be involved in alliin synthesis was obtained, the AcFMO had a cDNA of 1 374 bp and encoded 457 amino acids, which was evolutionarily closest to the AsFMO of garlic. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) indicated that AcFMO was the highest in the flowers and the lowest in the leaf sheaths. The results of subcellular localization showed that the AcFMO gene product was widely distributed throughout the cell A yeast expression vector was constructed, and the AcFMO gene was ecotopically overexpressed in yeast to further study the enzyme function in vitro and could catalyze the synthesis of alliin by S-allyl-l-cysteine. In summary, the cloning and functional identification of AcFMO have important reference value for understanding the biosynthesis of CSOs in onions.

Different methionine to cysteine supplementation ratios altered bone quality of broilers with or without Eimeria challenge assessed by dual energy X-ray absorptiometry and microtomography.

Despite the acknowledged significance of nutrition in bone development, effects of methionine (Met) and cysteine (Cys) on bone quality remain under-researched, particularly during Eimeria challenge. We investigated the effects of different supplemental Met to Cys ratios (MCR) on bone quality of broilers under Eimeria challenge. A total of 720 fourteen-day old Cobb500 broilers were allocated into a 5 × 2 factorial arrangement. Five diets with Met and Cys supplemented at MCR of 100:0, 75:25, 50:50, 25:75, and 0:100 were fed to the birds with or without Eimeria challenge. Body composition was measured by dual energy x-ray absorptiometry, and the femur bone characteristics were assessed by microtomography. Data were analyzed by two-way ANOVA and orthogonal polynomial contrast. The results reaffirmed the detrimental effects of Eimeria challenge on bone quality. On 9 d post inoculation (DPI), significant interaction effects were found for whole body bone mineral content (BMC), lean tissue weight, and body weight (P < 0.05); in the nonchallenged group (NCG), these parameters linearly decreased as MCR decreased (P < 0.05). In the challenged group (CG), body weight and lean tissue weight were unaffected by MCR, and BMC linearly increased as MCR decreased (P < 0.05). For the cortical bone of femoral metaphysis on 6 DPI, bone mineral density (BMD) linearly increased as MCR decreased (P < 0.05). Bone volume to tissue volume ratio (BV/TV) in the CG linearly increased as MCR decreased (P < 0.05). On 9 DPI, BMC and TV linearly increased as MCR decreased (P < 0.05) in the NCG. BMD and BV/TV changed quadratically as MCR decreased (P < 0.05). For the trabecular bone of femoral metaphysis on 9 DPI, BV/TV, and trabecular number linearly increased as MCR decreased (P < 0.05) in the NCG. For the femoral diaphysis, BV, TV, BMC on 6 DPI, and BMD on 9 DPI linearly increased as MCR decreased (P < 0.05). In conclusion, this study showed that both Eimeria challenge and varying supplemental MCR could influence bone quality of broilers.

Response of garlic (Allium sativum L.) to the combined toxicity of microplastics and arsenic.

The extensive utilization of mulch films in agricultural settings, coupled with the persistence of microplastic remnants in soil following the natural degradation of plastics, has given rise to detrimental microplastic impacts on crops. Arsenic (As) contamination in the environment is known to accumulate in crops through aquatic pathways or soil. Garlic (Allium sativum L.), a globally popular crop and seasoning, contains alliin, a precursor of its flavor compounds with medicinal properties. While alliin exhibits antimicrobial and antioxidant effects in garlic, its response to microplastics and arsenic has not been thoroughly investigated, specifically in terms of microplastic or As uptake. This study aimed to explore the impact of varied stress concentrations of microplastics on the toxicity, migration, and accumulation of As compounds. Results demonstrated that polystyrene (PS) fluorescent microspheres, with an 80 nm diameter, could permeate garlic bulbs through the root system, accumulating within vascular tissues and intercellular layers. Low concentrations of PS (10 and 20 mg L-1) and As (2 mg L-1) mitigated the production and accumulation of reactive oxygen species (ROS) and antioxidant enzymes in garlic. Conversely, garlic exhibited reduced root vigor, substance uptake, and translocation when treated with elevated As concentrations (4 mg L-1) in conjunction with PS concentrations of 40 and 80 mg L-1. An escalation in PS concentration facilitated As transport into bulbs but led to diminished As accumulation and biomass in the root system. Notably, heightened stress levels weakened garlic's antioxidant defense system, encompassing sulfur allicin and phytochelatin metabolism, crucial for combating the phytotoxicity of PS and As. In summary, PS exerted a detrimental influence on garlic, exacerbating As toxicity. The findings from this study offer insights for subsequent investigations involving Liliaceae plants.

Evaluating the Mechanism of Cell Death in Melanoma Induced by the Cannabis Extract PHEC-66.

Research suggests the potential of using cannabinoid-derived compounds to function as anticancer agents against melanoma cells. Our recent study highlighted the remarkable in vitro anticancer effects of PHEC-66, an extract from Cannabis sativa, on the MM418-C1, MM329, and MM96L melanoma cell lines. However, the complete molecular mechanism behind this action remains to be elucidated. This study aims to unravel how PHEC-66 brings about its antiproliferative impact on these cell lines, utilising diverse techniques such as real-time polymerase chain reaction (qPCR), assays to assess the inhibition of CB1 and CB2 receptors, measurement of reactive oxygen species (ROS), apoptosis assays, and fluorescence-activated cell sorting (FACS) for apoptosis and cell cycle analysis. The outcomes obtained from this study suggest that PHEC-66 triggers apoptosis in these melanoma cell lines by increasing the expression of pro-apoptotic markers (BAX mRNA) while concurrently reducing the expression of anti-apoptotic markers (Bcl-2 mRNA). Additionally, PHEC-66 induces DNA fragmentation, halting cell progression at the G1 cell cycle checkpoint and substantially elevating intracellular ROS levels. These findings imply that PHEC-66 might have potential as an adjuvant therapy in the treatment of malignant melanoma. However, it is essential to conduct further preclinical investigations to delve deeper into its potential and efficacy.

Oral intake of bucillamine, carvedilol, metformin, or phenformin does not protect against UVR-induced squamous cell carcinomas in hairless mice.

Squamous cell carcinoma represents the second most common type of keratinocyte carcinoma with ultraviolet radiation (UVR) making up the primary risk factor. Oral photoprotection aims to reduce incidence rates through oral intake of photoprotective compounds. Recently, drug repurposing has gained traction as an interesting source of chemoprevention. Because of their reported photoprotective properties, we investigated the potential of bucillamine, carvedilol, metformin, and phenformin as photoprotective compounds following oral intake in UVR-exposed hairless mice. Tumour development was observed in all groups in response to UVR, with only the positive control (Nicotinamide) demonstrating a reduction in tumour incidence (23.8%). No change in tumour development was observed in the four repurposed drug groups compared to the UV control group, whereas nicotinamide significantly reduced carcinogenesis (P = 0.00012). Metformin treatment significantly reduced UVR-induced erythema (P = 0.012), bucillamine and phenformin increased dorsal pigmentation (P = 0.0013, and P = 0.0005), but no other photoprotective effect was observed across the repurposed groups. This study demonstrates that oral supplementation with bucillamine, carvedilol, metformin, or phenformin does not affect UVR-induced carcinogenesis in hairless mice.

Accumulation of Sulforaphane and Alliin in Human Prostate Tissue.

Diets rich in cruciferous vegetables have been associated with a lower risk of incidence and progression of prostate cancer. Sulforaphane, an isothiocyanate derived from 4-methylsulphinylbutyl glucosinolate (glucoraphanin) that accumulates in certain of these vegetables, notably broccoli, has been implicated in their protective effects. Likewise, the consumption of garlic and its sulphur-containing compounds such as alliin have been associated with a reduction in risk of prostate cancer. In this study, we tested whether consuming glucoraphanin derived from broccoli seeds and alliin derived from garlic resulted in the occurrence of these potential bioactive compounds in the prostate, which may contribute to our understanding of the putative protective effects of these dietary components. We recruited 42 men scheduled for a trans-perineal prostate biopsy into a randomised, double-blinded, 2 × 2-factorial dietary supplement four-week intervention study, and 39 completed the study. The two active interventions were supplements providing glucoraphanin from broccoli (BroccoMax®) and alliin from garlic (Kwai Heartcare®). Following the intervention, prostate biopsy tissue was analysed for the presence of sulforaphane and its thiol conjugates and for alliin and associated metabolites. Sulforaphane occurred in significantly higher levels in the prostate tissue (both within the transition and peripheral zone) of men consuming the glucoraphanin containing supplements (p < 0.0001) compared to men not consuming these supplements. However, while alliin and alliin-derived metabolites were detected within the prostate, there was no significant difference in the concentrations of these compounds in the prostate of men consuming supplements derived from garlic compared to men not consuming these supplements.

The shortest innovative process for enhancing the S-allylcysteine content and antioxidant activity of black and golden garlic.

Black garlic is a type of heat-treated garlic for which the traditional process is extremely simple yet time-consuming, taking more than one month. The purpose of this research was to reduce the processing time of black garlic while maintaining a high level of S-allylcysteine (SAC), a black garlic quality indicator. The fresh garlic was pre-treated with CaCl2 and frozen before being further incubated at two different temperatures (60 and 80 °C) with a relative humidity of 65% and 80% RH. Results showed that sequential pre-treatment and incubation at 80 °C and 80% RH for 1 week yielded 874.26 mg of SAC/100 g dry weight with an antioxidant activity of 5390 and 25,421 mg Trolox/100 g for DPPH and ABTS assays, respectively. This process shortened the processing time of black garlic by about 4-times. The batch processed at 60 °C and 65% RH for 1 week provided the highest SAC content of about 1772 mg/100 g dry weight, which was 2-times higher than in incubation at 80 °C and 80% RH for 1 week. The colour of this garlic was golden, so we call this new processed garlic product "golden garlic".

Generation of garlic flavor after frying by infusing alliin into potato strips using pulsed electric field and assisted infusion methods.

A new method of alliin infusion into potato strips to generate garlic flavor upon frying was investigated. Potato strips were treated using pulsed electric field (PEF) and then allin was infused into the treated strips using immersion, ultrasound, or vacuum assisted infusion. Results showed that under lower PEF intensities (0.250, 0.650 and 1.250 kJ/kg), assisted infusion methods significantly improve alliin infusion efficiency (p < 0.05). The kinetics for alliin infusion showed that 1.250 kJ/kg PEF treatment and 35 kHz ultrasound assisted infusion have the highest a values of 94.69 and 94.80 (mg/mL.h), respectively. Scanning electron microscope (SEM) highlighted different cell structural changes before and after being treated with different PEF intensities and infusion methods. Sensory evaluations confirmed generation of garlic flavor upon frying (p < 0.05).

S-Allyl cysteine in garlic (Allium sativum): Formation, biofunction, and resistance to food processing for value-added product development.

S-allyl cysteine (SAC), which is the most abundant bioactive compound in black garlic (BG; Allium sativum), has been shown to have antioxidant, anti-apoptotic, anti-inflammatory, anti-obesity, cardioprotective, neuroprotective, and hepatoprotective activities. Sulfur compounds are the most distinctive bioactive elements in garlic. Previous studies have provided evidence that the concentration of SAC in fresh garlic is in the range of 19.0-1736.3 µg/g. Meanwhile, for processed garlic, such as frozen and thawed garlic, pickled garlic, fermented garlic extract, and BG, the SAC content increased to up to 8021.2 µg/g. BG is an SAC-containing product, with heat treatment being used in nearly all methods of BG production. Therefore, strategies to increase the SAC level in garlic are of great interest; however, further knowledge is required about the effect of processing factors and mechanistic changes. This review explains the formation of SAC in garlic, introduces its biological effects, and summarizes the recent advances in processing methods that can affect SAC levels in garlic, including heat treatment, enzymatic treatment, freezing, fermentation, ultrasonic treatment, and high hydrostatic pressure. Thus, the aim of this review was to summarize the outcomes of treatment aimed at maintaining or increasing SAC levels in BG. Therefore, publications from scientific databases in this field of study were examined. The effects of processing methods on SAC compounds were evaluated on the basis of the SAC content. This review provides information on the processing approaches that can assist food manufacturers in the development of value-added garlic products.

S-Allylcysteine Ameliorates Aging Features via Regulating Mitochondrial Dynamics in Naturally Aged C57BL/6J Mice.

SCOPE: S-Allylcysteine (SAC) is the most abundant organosulfur molecule derived from aged garlic. The effects ofSAC on improving Aging in naturally aged C57BL/6J male mice and mitochondrial dynamics in Caenorhabditis elegans and its underlying mechanisms is evaluated. METHODS AND RESULTS: When mice have attained reproductive senescence at 60 weeks of age, SAC is supplemented to 0.05% and 0.2% into their normal diet for 12 weeks. The results show that SAC could significantly improve the level of hepatic optic atrophy 1 (OPA1) mRNA, which is a key factor for mitochondrial fusion, and consequently elevated the mitochondrial biogenesis-related proteins sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), thus ameliorating oxidative stress, such as malondialdehyde (MDA) in the liver and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine. Among the biochemical markers of aging, SAC significantly reduces liver galactosidase ß1 (GLB1) and senescence-associated ß-galactosidase (SA-ßgal), which are induced by replicative senescence. The mitochondria with green fluorescent protein (GFP)-tagged transgenic strain SJ4103 C. elegans is incubated with 5 or 50 µM SAC, and SAC treated groups maintain the linear morphology of mitochondria. CONCLUSION: SAC regulates mitochondrial dynamics and ameliorated aging to a significant degree. This study also confirms that mitochondrial dynamics are a promising target for screening materials to combat aging and as a direction for anti-aging product development.

Alliin alleviates LPS-induced pyroptosis via promoting mitophagy in THP-1 macrophages and mice.

Pyroptosis is a new type of programmed cell death associated with inflammation. Excessive pyroptosis can cause body damage. Alliin is an organosulfur compound extracted from garlic, bearing anti-oxidation and anti-inflammatory properties. In this study, we revealed that alliin alleviated LPS-induced macrophage pyroptosis by detecting PI staining, IL-1ß and IL-18 release in vitro and in vivo. In the study of mechanism, we found that alliin might reduce the activation of NLRP3 inflammosome by decreasing intracellular ROS generation. Subsequently, we detected the effect of alliin on mitophagy which degraded damaged mitochondria. The results showed that alliin promoted PINK 1/Parkin-mediated mitophagy. After adding the mitophagy inhibitor CsA, the alleviating effect of alliin on mitochondrial damage and mitochondrial ROS were reversed and the relieving effect of alliin on LPS-induced pyroptosis was inhibited. These results suggested that alliin might reduce intracellular ROS production by promoting mitophagy, thus alleviating LPS-induced macrophages pyroptosis. Our study provides a new perspective and theoretical basis for alliin to alleviate pyroptosis which could further induce body damage.

D-ribose-L-cysteine modulates lead acetate-induced hematobiochemical alterations, hormonal imbalance, and ovarian toxicity in adult female Wistar rats.

Lead is a common environmental toxicant associated greatly with hematological and hormonal imbalance, biochemical alterations, and reproductive abnormalities. This study was conducted to evaluate the effects of D-ribose-L-cysteine (DRLC) on hematobiochemical and reproductive toxicity associated with lead acetate exposure in adult female Wistar rats. Thirty-two adult female Wistar rats (165 ± 20 g) were divided into four groups (n = 8). Group A received normal saline as placebo; Group B received 100 mg/kg BW of lead acetate only; Group C received 100 mg/kg BW of lead acetate and 10 mg/kg BW DRLC (low dose); Group D received 100 mg/kg BW of lead acetate and 30 mg/kg BW of DRLC (high dose). All administration was done via oral gavage for 42 days, thereafter animals were sacrificed; serum was obtained from the blood collected for analysis, ovaries, and uterus was harvested for analysis. The lead acetate only group showed a significant difference in hematological indices relative to control. Additionally, there was a significant decrease in body weight, sodium dismutase, catalase, reduced glutathione, progesterone with a corresponding increase in ovarian weight, MDA, FSH, and LH among the lead acetate only group relative to the control. Histological observation showed atretic antral follicles, with detached granulosa cells, pyknotic nuclei in the granulosa wall in the ovaries of the lead-exposed only group compared to the control. Co-administration of DRLC and lead attenuate the toxicity of lead exposure by restoring the hematological values, biochemical parameters, hormone profile, and morphology of the ovary. Exposure to lead acetate causes deleterious toxicity to hematological and reproductive functions which were ameliorated DRLC supplementation through its antioxidant mechanisms.

In silicoinvestigation of Alliin as potential activator for AMPA receptor.

Natural products from plants, such as flavonoids, arouse immense interest in medicine because of the therapeutic and many other bioactive properties. The molecular docking is a very useful method to screen the molecules based on their free binding energies and give important structural suggestions about how molecules might activate or inhibit the target receptor by comparing reference molecules. Alliin and Allicin differ from many other flavonoids because of containing no benzene rings and having nitrogen and sulfur atoms in their structure. In this study Alliin and Allicin affinity on AMPA, NMDA and GABA-A receptors were evaluated in the central nervous system by using the molecular docking method. Both Alliin and Allicin indicated no inhibitory effects. However Alliin showed significant selectivity to human AMPA receptor (3RN8) as an excitatory. The binding energy of glutamate to 3RN8 was -6.61 kcal mol-1, while the binding energy of Allin was -8.08 kcal mol-1. Furthermore Alliin's affinity to the other AMPA and NMDA receptors is quite satisfactory compared to the reference molecule glutamate. In conclusion based on the molecular docking study, Alliin can be useful for synaptic plasticity studies whereas might be enhance seizure activity because of the increased permeability to cations. It also can be beneficial to improve learning and memory and can be used as a supportive product to the hypofunction of NMDA associated problems.

S-1-Propenylcysteine promotes IL-10-induced M2c macrophage polarization through prolonged activation of IL-10R/STAT3 signaling.

Atherosclerosis is a chronic inflammatory disease that may lead to the development of serious cardiovascular diseases. Aged garlic extract (AGE) has been reported to ameliorate atherosclerosis, although its mode of action remains unclear. We found that AGE increased the mRNA or protein levels of arginase1 (Arg1), interleukin-10 (IL-10), CD206 and hypoxia-inducible factor 2α (HIF2α) and decreased that of CD68, HIF1α and inducible nitric oxide synthase in the aorta and spleen of apolipoprotein E knockout mice. We also found that S-1-propenylcysteine (S1PC), a characteristic sulfur compound in AGE, increased the level of IL-10-induced Arg1 mRNA and the extent of M2c-like macrophage polarization in vitro. In addition, S1PC increased the population of M2c-like macrophages, resulting in suppressed the population of M1-like macrophages and decreased lipopolysaccharide-induced production of pro-inflammatory cytokines. These effects were accompanied by prolonged phosphorylation of the IL-10 receptor α (IL-10Rα) and signal transducer and activator of transcription 3 (STAT3) that inhibited the interaction between IL-10Rα and Src homology-2-containing inositol 5'-phosphatase 1 (SHIP1). In addition, administration of S1PC elevated the M2c/M1 macrophage ratio in senescence-accelerated mice. These findings suggest that S1PC may help improve atherosclerosis due to its anti-inflammatory effect to promote IL-10-induced M2c macrophage polarization.

Comparison of perfusion 18F-FP-CIT PET and 99mTc-ECD SPECT in parkinsonian disorders.

ABSTRACT: Early and accurate identification of various conditions that can cause parkinsonian symptoms is important for determining treatment policies. Currently dopamine transporter (DAT) imaging using FP-CIT, glucose metabolism imaging using fluorodeoxyglucose, cerebral blood flow image using ethyl cysteinate dimer (ECD), and others are used for differentiation. However, the use of multiple modalities is inconvenient and costly. In the present retrospective study, we evaluated the correlation between regional brain uptake ratios (URs) in perfusion FP-CIT PET and ECD SPECT images.Twenty patients with Parkinson's symptoms underwent perfusion DAT positron emission tomography (18F-FP-CIT PET/CT) and cerebral blood flow tomography (99mTc-ECD SPECT) within a 2-week period. Perfusion 18F-FP-CIT PET/CT and 99mTc-ECD SPECT URs of 19 brain regions (bilateral frontal, temporal, parietal and occipital lobes, bilateral caudate nucleus, bilateral putamen, bilateral insula, bilateral cingulate gyrus, bilateral thalamus, and brainstem) were directly compared and correlations were analyzed.Average 18F-FP-CIT PET/CT regional perfusion URs were higher than 99mTc-ECD SPECT URs. Uptake ratios were well correlated in all 19 regions (except right putamen), and especially in dopamine poor regions (cerebral cortex). In left putamen, URs were significantly correlated, but the correlation coefficient was lower than those of other regions.A single tracer dual phase N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane test seems to be helpful for differential diagnosis of parkinsonian disorders. Large-scale, longitudinal studies on complementary diseases with parkinsonian patterns are required to investigate differences in correlations between perfusion 18F-FP-CIT PET/CT and 99mTc-ECD SPECT over time.

S-methyl cysteine sulfoxide mitigates histopathological damage, alleviate oxidative stress and promotes immunomodulation in diabetic rats.

OBJECTIVES: S-methyl cysteine sulfoxide (SMCS) is a hydrophilic cysteine-containing natural compound found in plants and is known to possess antidiabetic and antioxidant properties. We investigated the antioxidant and immunomodulatory properties of SMCS, as well as histopathological changes in the liver and pancreas in streptozotocin (STZ)-induced diabetic rats. METHODS: The rats were divided into the following groups: control (CG), comprising non-diabetic rats; STZ-DB, comprising STZ-induced diabetic rats; and STZ-SMCS, comprising STZ-induced diabetic rats treated with SMCS. SMCS (200 mg/kg) was administered by gavage daily for 30 days. Biochemical and cytokine analyses, catalase (CAT) and superoxide dismutase (SOD) activities assays and histopathological analysis of liver and pancreas tissues were performed. RESULTS: SMCS treatment reduced glycemia (p<0.05), decreased triglyceride (p<0.01) and very-low-density lipoprotein (VLDL) levels (p<0.01), and increased SOD and CAT activity in the liver (both p<0.01) compared with STZ-DB group. Higher activity values of IL-10 were observed in the STZ-SMCS group than in the other groups (p<0.001). Liver glycogen was significantly improved in the STZ-SMCS group compared with the STZ-DB group. SMCS also ameliorated damage to pancreatic islets, which resulted in restoration of their morphology. CONCLUSIONS: Oral treatment of SMCS showed improvement of the morphological alterations in liver and pancreatic islet in diabetic rats. These beneficial morphological effects of SMCS can be partially explained by IL-10 modulation associated with antioxidant action.

Safety and efficacy of spleen aminopeptide oral lyophilized powder for improving quality of life and immune response in patients with advanced breast cancer: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Health-related quality of life (HRQoL) is an important consideration in managing patients. Spleen aminopeptide oral lyophilized powder (SAOLP) has been used to enhance cellular immunity in a patient. This multicenter, randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the safety and efficacy of SAOLP for improving HRQoL in patients with breast cancer. Patients diagnosed with advanced breast cancer were included, and were administered SAOLP or placebo 4 mg qd for two cycles. The primary endpoint was improvement in HRQoL on day 42 measured by the EORTC QLQ-C30 and EORTC QLQ-BR23. Secondary endpoints included immunologic function, improvement in HRQoL on day 21 and 84, objective response rate, disease control rate, BMI and adverse events. On day 42, on the EORTC QLQ-C30 or EORTC QLQ-BR23, scores on the functional scales and QoL scale were significantly higher and scores on symptom scales were significantly lower in patients who received SAOLP compared to placebo (P < 0.05). On day 84, the number of CD3, CD4 and CD8 cells were significantly higher in patients who received SAOLP. There were no significant differences in objective response rate, disease control rate or BMI. SAOLP may improve HRQoL and the immune response in patients with advanced breast cancer, represents a convenient and safe adjuvant therapy.

Onion component, isoalliin, stimulates feeding and activates the arcuate nucleus neuropeptide Y, ghrelin- and Ninjin'yoeito-responsive neurons.

Appetite loss or anorexia substantially decreases the quality of life in patients with cancer, depression and gastrointestinal disorders, and can lead to sarcopenia and frailty. Foods that restore appetite have been sought-for but are not currently available. Historically, onion intake was adopted to treat a variety of diseases with reduced appetite including cancer and gastrointestinal disturbances. While isoalliin is a core component of onion, the effects of isoalliin on feeding behavior and feeding centers remain unknown. Neuropeptide Y (NPY) and ghrelin are the most potent central and peripheral inducers of appetite. A Japanese kampo medicine Ninjin'yoeito activates ghrelin-responsive NPY neurons in the hypothalamic arcuate nucleus (ARC) and counteracts anorexia induced by an anti-cancer drug cisplatin. This study explored the effects of isoalliin on feeding behavior and activities of ARC neurons in mice. Isoalliin, injected intraperitoneally, dose-dependently increased food intake during dark phase (DP) and daily without altering light phase (LP) food intake. We measured cytosolic Ca2+ concentration ([Ca2+]i) in single ARC neurons including NPY neurons identified by GFP fluorescence. Isoalliin increased [Ca2+]i in 10 of 18 (55.6%) NPY neurons, a majority of which also responded to ghrelin with [Ca2+]i increases, indicating that the ARC ghrelin-responsive NPY neuron is the major target of isoalliin. Isoalliin also increased [Ca2+]i in the ARC neurons that responded to Ninjin'yoeito. These results indicate that isoalliin enhances feeding at the active period and activates ARC ghrelin-responsive NPY neurons and Ninjin'yoeito-responsive neurons. These abilities of isoalliin to stimulate DP feeding and activate ARC orexigenic neurons provide scientific evidence for the health beneficial effects of onion experienced historically and globally.

Cytoprotective Potential of Aged Garlic Extract (AGE) and Its Active Constituent, S-allyl-l-cysteine, in Presence of Carvedilol during Isoproterenol-Induced Myocardial Disturbance and Metabolic Derangements in Rats.

This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.

A novel dendritic mesoporous silica based sustained hydrogen sulfide donor for the alleviation of adjuvant-induced inflammation in rats.

PURPOSE: S-propargyl-cysteine (SPRC), an excellent endogenous hydrogen sulfide (H2S) donor, could elevate H2S levels via the cystathionine γ-lyase (CSE)/H2S pathway both in vitro and in vivo. However, the immediate release of H2S in vivo and daily administration of SPRC potentially limited its clinical use. METHODS: To solve the fore-mentioned problem, in this study, the dendritic mesoporous silica nanoparticles (DMSN) was firstly prepared, and a sustained H2S delivery system consisted of SPRC and DMSN (SPRC@DMSN) was then constructed. Their release profiles, both in vitro and in vivo, were investigated, and their therapeutical effect toward adjuvant-induced arthritis (AIA) rats was also studied. RESULTS: The spherical morphology of DMSN could be observed under scanning Electron Microscope (SEM), and the transmission electron microscope (TEM) images showed a central-radiational pore channel structure of DMSN. DMSN showed excellent SPRC loading capacity and attaining a sustained releasing ability than SPRC both in vitro and in vivo, and the prolonged SPRC releasing could further promote the release of H2S in a sustained manner through CSE/H2S pathway both in vitro and in vivo. Importantly, the SPRC@DMSN showed promising anti-inflammation effect against AIA in rats was also observed. CONCLUSIONS: A sustained H2S releasing donor consisting of SPRC and DMSN was constructed in this study, and this sustained H2S releasing donor might be of good use for the treatment of AIA.