Inflammatory bowel diseases (IBD), which include Crohn\'s disease and ulcerative colitis, manifest as a result of intricate interactions involving genetic predisposition, environmental factors, intestinal microbiota dynamics, and immune dysregulation, ultimately leading to persistent mucosal inflammation. Addressing this complex pathology requires a nuanced understanding to inform targeted therapeutic strategies. Consequently, our study explored the viability of Aged Garlic Extract (AGE) as an alternative therapeutic regimen for IBD management. Utilizing gas chromatography-mass spectrometry (GC-MS) and scanning electron microscopy (SEM), we characterized AGE, revealing distinctions from Fresh Garlic Extract (FGE), particularly the absence of allicin in AGE and accompanying structural alterations. In In-Vivo experiments employing an IBD rat model, AGE intervention exhibited remarkable antioxidant, antibacterial, and anti-inflammatory properties. Noteworthy outcomes included improved survival rates, mitigation of intestinal damage, restoration of gut microbial diversity, reinforcement of tight junctions, and reversal of mitochondrial dysfunction. Collectively, these effects contributed to the preservation of enterocyte integrity and the attenuation of inflammation. In conclusion, the unique chemical composition of AGE, coupled with its substantial influence on gut microbiota, antioxidant defenses, and inflammatory pathways, positions it as a promising adjunctive therapy for the management of IBD. These observations, synergistically considered with existing research, provide significant insights into the potential utility of AGE in addressing the intricate pathophysiology inherent to IBD. The potential strength of study and rationale of using AGE against IBD includes exploring alternative therapeutic regimens if conventional treatments are associated with side effects, identification of potential hotspots/pathways involved in disease progression and study can provide economically cheaper and naturally occurring alternative to patient community who are struggling to afford expensive medications. These promising findings underscore the necessity for additional investigations to ascertain the feasibility of clinical translation, thereby substantiating the potential therapeutic role of AGE in the management of IBD.

In the tumor treatment by Fenton reaction‒based nanocatalytic medicines, the gradual consumption of Fe(II) ions greatly reduces the production of hydroxyl radicals, one of the most active reactive oxygen species (ROS), leading to much deteriorated therapeutic efficacy. Meanwhile, the ROS consumption caused by the highly expressed reduced glutathione (GSH) in the tumor microenvironment further prevents tumor apoptosis. Therefore, using the highly expressed GSH in tumor tissue to promote the Fe(III) reduction to Fe(II) can not only weaken the resistance of tumor to ROS attack, but also generate enough Fe(II) to accelerate the Fenton reaction. In view of this, an allicin‒modified FeO1-xOH nanocatalyst possessing varied valence states (II, III) has been designed and synthesized. The coexistence of Fe(II)/Fe(III) enables the simultaneous occurrence of Fenton reaction and GSH oxidation, and the Fe(III) reduction by GSH oxidation results in the promoted cyclic conversion of Fe ions in tumor and positive catalytic therapeutic effects. Moreover, allicin capable of regulating cell cycle and suppressing tumor growth is loaded on FeO1-xOH nanosheets to activate immune response against tumors and inhibit tumor recurrence, finally achieving the tumor regression efficiently and sustainably. This therapeutic strategy provides an innovative approach to formulate efficient antitumor nanomedicine for enhanced tumor treatment.

Cardiovascular disease (CVD) remains the predominant cause of mortality and disability worldwide. Against this backdrop, finding effective drugs for the pharmacological treatment of CVD has become one of the most urgent and challenging issues in medical research. Garlic (Allium sativum L.) is one of the oldest plants and is world-renowned for its dietary and medicinal values. Allicin (diallyl thiosulfinate) is one of the primary natural active ingredients in garlic, which has been proven to have powerful cardioprotective effects and mediate various pathological processes related to CVD, such as inflammatory factor secretion, myocardial cell apoptosis, oxidative stress, and more. Therefore, allicin holds a promising application prospect in the treatment of CVD. This review summarized the biological functions of allicin and its potential mechanisms in CVD, including antioxidation, anti-inflammation, and anti-apoptosis effects. Reckoning with these, we delved into recent studies on allicin\'s cardioprotective effects concerning various CVDs, such as atherosclerosis, hypertension, myocardial infarction, arrhythmia, cardiac hypertrophy, heart failure, and cardiotoxicity. Further, considering the tremendous advancement in nanomedicine, nanotechnology-based drug delivery systems show promise in addressing limitations of allicin\'s clinical applications, including improving its solubility, stability, and bioavailability. Through this review, we hope to provide a reference for further research on allicin in cardioprotection and drug development.

UNASSIGNED: To analyze the effect of allicin on the immunoreactivity of osteosarcoma (OS) cells and further explore whether its mechanism is related to the long non-coding Ribonucleic Acid (lncRNA) CBR3-AS1/miR-145-5p/GRP78 axis, so as to provide clinical evidence.
UNASSIGNED: The human OS cell line Saos-2 was treated with allicin at 25, 50, and 100 μmol/L, respectively, to observe changes in cell biological behaviors. Subsequently, CBR3-AS1 abnormal expression vectors were constructed and transfected into Saos-2 to discuss their influence on OS. Furthermore, the regulatory relationship between allicin and the CBR3-AS1/miR-145-5p/GRP78 axis was validated by rescue experiments. Finally, a nude mice tumorigenesis experiment was carried out to analyze the effects of allicin and CBR3-AS1/miR-145-5p/GRP78 axis on the growth of living tumors. Alterations in T-lymphocyte subsets were also detected to assess the effect of allicin on OS immunoreactivity.
UNASSIGNED: With the increase of allicin concentration, Saos-2 activity decreased and apoptosis increased (P < 0.05). In addition, the expression of CBR3-AS1 and GRP78 decreased after allicin intervention, while miR-145-5p increased (P < 0.05). Silencing CBR3-AS1 led to reduced Saos-2 activity, enhanced apoptosis, and activated mitophagy and endoplasmic reticulum stress (P < 0.05). In the rescue experiment, the effect of CBR3-AS1 on OS cells was reversed by silencing miR-145-5p, while the impact of miR-145-5p was reversed by GRP78. Finally, the tumorigenesis experiment in nude mice confirmed the regulatory effects of allicin and CBR3-AS1/miR-145-5p/GRP78 on tumor growth in vivo. Meanwhile, it was seen that allicin activated CD4+CD8+ in OS mice, confirming that allicin has the effect of activating OS immunoreactivity.
UNASSIGNED: Allicin activates OS immunoreactivity and induces apoptosis through the CBR3-AS1/miR-145-5p/GRP78 molecular axis.

Aflatoxin B1 (AFB1) is known to inhibit growth, and inflict hepatic damage by interfering with protein synthesis. Allicin, has been acknowledged as an efficacious antioxidant capable of shielding the liver from oxidative harm. This study aimed to examine the damage caused by AFB1 on bovine hepatic cells and the protective role of allicin against AFB1-induced cytotoxicity. In this study, cells were pretreated with allicin before the addition of AFB1 for co-cultivation. Our findings indicate that AFB1 compromises cellular integrity, suppresses the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, allicin attenuates oxidative damage to bovine hepatic cells caused by AFB1 by promoting the expression of the Nrf2 pathway and reducing cell apoptosis. In conclusion, the results of this study will help advance clinical research and applications, providing new options and directions for the prevention and treatment of liver diseases.

Limited alliinase resources cause difficulties in the biosynthesis of thiosulfinates (e.g., allicin), restricting their applications in the agricultural and food industries. To effectively biosynthesize thiosulfinates, this study aimed to excavate bacterial alliinase resources and elucidate their catalytic properties. Two bacterial cystathionine β-lyases (MetCs) possessing high alliinase activity (>60 U mg -1) toward L-(-)-alliin were identified from Allium sativum rhizosphere isolates. Metagenomic exploration revealed that cystathionine β-lyase from Bacillus cereus (BcPatB) possessed high activity toward both L-(±)-alliin and L-(+)-alliin (208.6 and 225.1 U mg -1), respectively. Although these enzymes all preferred l-cysteine S-conjugate sulfoxides as substrates, BcPatB had a closer phylogenetic relationship with Allium alliinases and shared several similar features with A. sativum alliinase. Interestingly, the Trp30Ile31Ala32Asp33 Met34 motif in a cuspate loop of BcPatB, especially sites 31 and 32 at the top of the motif, was modeled to locate near the sulfoxide of L-(+)-alliin and is important for substrate stereospecificity. Moreover, the stereoselectivity and activity of mutants I31V and A32G were higher toward L-(+)-alliin than those of mutant I31L/D33E toward L-(-)-alliin. Using bacterial alliinases and chemically synthesized substrates, we obtained thiosulfinates with high antimicrobial and antinematode activities that could provide insights into the protection of crops and food.

The global burden of liver disease is enormous, which highlights the need for effective hepatoprotective agents. It was reported that allicin exhibits protective effects against a range of diseases. In this study, we further evaluated allicin\'s effect and mechanism in acute hepatic injury. Liver injury in mice was induced by intraperitoneal injection with 1% CCl4 (10 mL/kg/day). When the first dose was given, CCl4 was given immediately after administration of different doses of allicin (40, 20, and 10 mg/kg/day) as well as compound glycyrrhizin (CGI, 80 mg/kg/day), and then different doses of allicin (40, 20, and 10 mg/kg/day) as well as compound glycyrrhizin (CGI, 80 mg/kg/day) were administrated every 12 h. The animals were dissected 24 h after the first administration. The findings demonstrated a significant inhibition of CCl4-induced acute liver injury following allicin treatment. This inhibition was evidenced by notable reductions in serum levels of transaminases, specifically aspartate transaminase, along with mitigated histological damage to the liver. In this protective process, allicin plays the role of reducing the amounts or the expression levels of proinflammatory cytokines, IL-1β, IL-6. Furthermore, allicin recovered the activities of the antioxidant enzyme catalase (CAT) and reduced the production of malondialdehyde (MDA) in a dose-dependent manner, and also reduced liver Caspase 3, Caspase 8, and BAX to inhibit liver cell apoptosis. Further analysis showed that the administration of allicin inhibited the increased protein levels of Nuclear factor-erythroid 2-related factor 2 (Nrf2) and NAD(P)H:quinone oxidoreductase 1 (NQO1), which is related to inflammation and oxidative stress. The in vitro study of the LPS-induced RAW264.7 inflammatory cell model confirmed that allicin can inhibit important inflammation-related factors and alleviate inflammation. This research firstly clarified that allicin has a significant protective effect on CCl4-induced liver injury via inhibiting the inflammatory response and hepatocyte apoptosis, alleviating oxidative stress associated with the progress of liver damage, highlighting the potential of allicin as a hepatoprotective agent.

BACKGROUND: Allicin regulates macrophage autophagy and senescence, and inhibits hepatoma cell growth. This study investigated the mechanism by which allicin inhibits the growth of hepatoma cells.
METHODS: Hepa1-6 mouse hepatoma cells were subcutaneously injected into C57BL/6 J mice to construct a tumor transplantation model. Macrophages were cultured with the supernatant of hepatoma cells to construct a cell model. The levels of mRNA and proteins and the level of Sestrin2 ubiquitination were measured by RTqPCR, immunofluorescence and Western blotting. The levels of autophagy-related factors and the activity of senescence-associated β-galactosidase were determined by kits, and protein stability was detected by cycloheximide (CHX) tracking.
RESULTS: Data analysis of clinical samples revealed that RBX1 was highly expressed in tumor tissues, while Sestrin2 was expressed at low levels in tumor tissues. Allicin can promote the expression of the autophagy-related proteins LC3 and Beclin-1 in tumor macrophages and inhibit the expression of the aging-related proteins p16 and p21, thus promoting autophagy in macrophages and inhibiting cell senescence. Moreover, allicin can inhibit the expression of RBX1, thereby reducing the ubiquitination of Sestrin2, enhancing the stability of Sestrin2, activating autophagy in tumor macrophages and inhibiting senescence. In addition, allicin treatment inhibited the proliferation and migration of hepatoma carcinoma cells cocultured with macrophages and significantly improved the development of liver cancer in mice.
CONCLUSIONS: Allicin can affect the autophagy of macrophages and restrain the growth of hepatoma cells by regulating the ubiquitination of Sestrin2.

Allicin is a safe herbal extract believed to have antitumor effects, which, however, remain unclear. The aim of the present work was to discuss Allicin antitumor effects on cervical cancer using cell experiments. Using Hela and Siha to our research objectives in our study, first step, difference concentration of Allicin (20, 40, and 80 μM) treated Hela and Siha cell lines, and next step, discuss circEIF4G2 effects in Allicin antitumor effects in Hela and Siha cell lines; the cell proliferation and EdU-positive cell number by CCK-8 and EdU staining; cell apoptosis rate by flow cytometry; invasion cell number by transwell assay; wound healing rate by wound healing assay; and relative mRNA and protein levels using qRT-PCR and WB assay. With Allicin supplement, the cell proliferation and EdU-positive cell number were significantly depressed with cell apoptosis rate significantly increasing; invasion cell number and wound healing rate significantly suppressed with circEIF4G2 mRNA expression significantly down-regulation (p < .05, respectively). However, there was no significant difference among Allicin, si-circEIF4G2, and Allicin+si-circEIF4G2 in cell biological activities including cell proliferation, apoptosis, invasion and migration, and relative gene and protein expression. Allicin depresses biological activities of cervical cancer cells through down-regulating circEIF4G2/HOXA1/AKT/mTOR.

The transmission of manure- and wastewater-borne antibiotic-resistant bacteria (ARB) to plants contributes to the proliferation of antimicrobial resistance in agriculture, necessitating effective strategies for preventing the spread of antibiotic resistance genes (ARGs) from ARB in the environment to humans. Nanomaterials are potential candidates for efficiently controlling the dissemination of ARGs. The present study investigated the abundance of ARGs in hydroponically grown garlic (Allium sativum L.) following nano-CeO2 (nCeO2) application. Specifically, root exposure to nCeO2 (1, 2.5, 5, 10 mg L-1, 18 days) reduced ARG abundance in the endosphere of bulbs and leaves. The accumulation of ARGs (cat, tet, and aph(3\')-Ia) in garlic bulbs decreased by 24.2-32.5 % after nCeO2 exposure at 10 mg L-1. Notably, the lignification extent of garlic stem-disc was enhanced by 10 mg L-1 nCeO2, thereby accelerating the formation of an apoplastic barrier to impede the upward transfer of ARG-harboring bacteria to garlic bulbs. Besides, nCeO2 upregulated the gene expression related to alliin biosynthesis and increased allicin content by 15.9-16.2 %, promoting a potent antimicrobial defense for reducing ARG-harboring bacteria. The potential exposure risks associated with ARGs and Ce were evaluated according to the estimated daily intake (EDI). The EDI of ARGs exhibited a decrease exceeding 95 %, while the EDI of Ce remained below the estimated oral reference dose. Consequently, through stimulating physical and chemical defenses, nCeO2 contributed to a reduced EDI of ARGs and Ce, highlighting its potential for controlling ARGs in plant endosphere within the framework of nano-enabled agrotechnology.