Garlic and Hypertension: Efficacy, Mechanism of Action, and Clinical Implications.

Hypertension is a major risk factor for heart disease and stroke. Garlic has a long history of use in traditional medicine for various conditions, including hypertension. This narrative review examined the scientific evidence on the efficacy of garlic in lowering blood pressure. It explores the historical uses of garlic in different cultures for medicinal purposes and delves into the phytochemical composition of garlic, highlighting key components, like allicin and ajoene, that are believed to contribute to its potential health benefits. Clinical studies that investigated the effects of garlic and garlic-based supplements on blood pressure are presented, with the findings suggesting that garlic consumption may modestly reduce blood pressure, particularly in individuals with mild hypertension. Potential mechanisms of action include increased nitric oxide production, improved endothelial function, and antioxidant properties. While garlic may offer some benefits for blood pressure management, it should not be considered a substitute for conventional antihypertensive medications. Further large-scale, long-term clinical trials are warranted to establish the efficacy of garlic in managing hypertension, including the optimal dosage and formulation.

Which Constituents Determine the Antioxidant Activity and Cytotoxicity of Garlic? Role of Organosulfur Compounds and Phenolics.

Garlic is a vegetable with numerous pro-health properties, showing high antioxidant capacity, and cytotoxicity for various malignant cells. The inhibition of cell proliferation by garlic is mainly attributed to the organosulfur compounds (OSCs), but it is far from obvious which constituents of garlic indeed participate in the antioxidant and cytotoxic action of garlic extracts. This study aimed to obtain insight into this question by examining the antioxidant activity and cytotoxicity of six OSCs and five phenolics present in garlic. Three common assays of antioxidant activity were employed (ABTS● decolorization, DPPH● decolorization, and FRAP). Cytotoxicity of both classes of compounds to PEO1 and SKOV-3 ovarian cancer cells, and MRC-5 fibroblasts was compared. Negligible antioxidant activities of the studied OSCs (alliin, allicin, S-allyl-D-cysteine, allyl sulfide, diallyl disulfide, and diallyl trisulfide) were observed, excluding the possibility of any significant contribution of these compounds to the total antioxidant capacity (TAC) of garlic extracts estimated by the commonly used reductive assays. Comparable cytotoxic activities of OSCs and phenolics (caffeic, p-coumaric, ferulic, gallic acids, and quercetin) indicate that both classes of compounds may contribute to the cytotoxic action of garlic.

Allicin Mitigates Diabetic Retinopathy in Rats by Activating Phosphatase and Tensin Homolog-induced Kinase 1/Parkin-mitophagy and Inhibiting Oxidative Stress-mediated NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome.

ABSTRACT: Diabetic retinopathy (DR) is one of the significant disabling outcomes of diabetes mellitus characterized by retinal microvascular damage, inflammation, and neuronal dysfunction. Allicin (Alc), a natural compound found in garlic, has garnered attention for its antioxidant and anti-inflammatory properties, positioning it as a potential therapeutic agent for DR. The aim of the present study was to investigate the therapeutic efficacy of Alc in DR management and elucidate its underlying mechanisms of action. We established a DR model in male Sprague-Dawley rats (n = 50, 200-250 g, 12 weeks old) using a high-fat diet for 8 weeks plus a low dose of streptozotocin administered at the start of the 4th week. The diabetic (Diab) animals were administered Alc (16 mg/kg/day, orally), either alone or in combination with mitochondrial division inhibitor-1 (Mdivi-1) as a mitophagy inhibitor, starting 28 days before tissue sampling. We evaluated histopathological changes, metabolic abnormalities associated with type 2 diabetes mellitus (T2DM), the expression of proteins regulating pyroptosis (NOD-like receptor family pyrin domain containing 3, cleaved-caspase 1, and gasdermin D-N terminal) and mitophagy (phosphatase and tensin homolog-induced kinase 1 [PINK1] and Parkin), as well as the levels of oxidative stress mediators and proinflammatory cytokines. Alc treatment effectively ameliorated histopathological changes and metabolic abnormalities associated with T2DM. It downregulated pyroptosis-related proteins, upregulated mitophagy-related proteins, reduced proinflammatory cytokine levels, and attenuated oxidative stress. Treatment with Mdivi-1 suppressed the beneficial effects of Alc. Our findings highlight the therapeutic potential of Alc in managing DR by targeting multiple pathophysiological pathways, including pyroptosis, inflammation, and oxidative stress. The observed antipyroptotic effects of Alc were partially mediated by the activation of the PINK1/parkin-mediated mitophagy pathway. Additional studies are necessary to thoroughly understand the therapeutic mechanisms of Alc and its viability as a treatment choice for DR.

Allicin‒Decorated FeO1-xOH Nanocatalytic Medicine for Fe2+/Fe3+ Cycling‒Promoted Efficient and Sustained Tumor Regression.

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.

Allicin: a promising modulator of apoptosis and survival signaling in cancer.

According to the World Health Organization, cancer is the foremost cause of mortality globally. Various phytochemicals from natural sources have been extensively studied for their anticancer properties. Allicin, a powerful organosulfur compound derived from garlic, exhibits anticancer, antioxidant, anti-inflammatory, antifungal, and antibacterial properties. This review aims to update and evaluate the chemistry, composition, mechanisms of action, and pharmacokinetics Allicin. Allicin has garnered significant attention for its potential role in modulating Fas-FasL, Bcl2-Bax, PI3K-Akt-mTOR, autophagy, and miRNA pathways. At the molecular level, allicin induces the release of cytochrome c from the mitochondria and enhances the activation of caspases-3, -8, and -9. This is accompanied by the simultaneous upregulation of Bax and Fas expression in tumor cells. Allicin can inhibit excessive autophagy by activating the PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Allicin-loaded nano-formulations efficiently induce apoptosis in cancer cells while minimizing toxicity to normal cells. Safety and clinical aspects are meticulously scrutinized, providing insights into the tolerability and adverse effects associated with allicin administration, along with an overview of current clinical trials evaluating its therapeutic potential. In conclusion, this review underscores the promising prospects of allicin as a dietary-derived medicinal compound for cancer therapy. It emphasizes the need for further research to elucidate its precise mechanisms of action, optimize delivery strategies, and validate its efficacy in clinical settings.

Allicin inhibits the growth of HONE-1 and HNE1 human nasopharyngeal carcinoma cells by inducing ferroptosis.

Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.

Cellular uptake of allicin in the hCMEC/D3 human brain endothelial cells: exploring blood-brain barrier penetration in an in vitro model.

Background: Allicin, a bioactive compound derived from garlic (Allium sativum), demonstrates antibacterial activity against a broad spectrum of bacteria including the most common meningitis pathogens. In order to advocate for allicin as a potential therapeutic candidate for bacterial meningitis, the present study aimed to assess the ability of allicin to cross the blood-brain barrier (BBB) using an in vitro model. Methods: The cell viability of the human brain endothelial cell line hCMEC/D3 after incubation with various concentrations of allicin was investigated using an MTT assay at 3 and 24 h. Additionally, reactive oxygen species (ROS) production of allicin-treated hCMEC/D3 cells was examined at 3 h. The concentrations of allicin that were not toxic to the cells, as determined by the MTT assay, and did not significantly increase ROS generation, were then used to investigate allicin's ability to traverse the in vitro BBB model for 3 h. High-performance liquid chromatography (HPLC) analysis was utilized to examine the allicin concentration capable of passing the in vitro BBB model. The cellular uptake experiments were subsequently performed to observe the uptake of allicin into hCMEC/D3 cells. The pkCSM online tool was used to predict the absorption, distribution, metabolism, excretion, and pharmacokinetic properties of allicin and S-allylmercaptoglutathione (GSSA). Results: The results from MTT assay indicated that the highest non-toxicity concentration of allicin on hCMEC/D3 cells was 5 µg/ml at 3 h and 2 µg/ml at 24 h. Allicin significantly enhanced ROS production of hCMEC/D3 cells at 10 µg/ml at 3 h. After applying the non-toxicity concentrations of allicin (0.5-5 µg/ml) to the in vitro BBB model for 3 h, allicin was not detectable in both apical and basolateral chambers in the presence of hCMEC/D3 cells. On the contrary, allicin was detected in both chambers in the absence of the cells. The results from cellular uptake experiments at 3 h revealed that hCMEC/D3 cells at 1 × 104 cells could uptake allicin at concentrations of 0.5, 1, and 2 µg/ml. Moreover, allicin uptake of hCMEC/D3 cells was proportional to the cell number, and the cells at 5 × 104 could completely uptake allicin at a concentration of 5 µg/ml within 0.5 h. The topological polar surface area (TPSA) predicting for allicin was determined to be 62.082 Å2, indicating its potential ability to cross the BBB. Additionally, the calculated logBB value surpassing 0.3 suggests that the compound may exhibit ease of penetration through the BBB. Conclusion: The present results suggested that allicin was rapidly taken up by hCMEC/D3 cells in vitro BBB model. The prediction results of allicin's distribution patterns suggested that the compound possesses the capability to enter the brain.

Allicin attenuates the oxidative damage induced by Aflatoxin B1 in dairy cow hepatocytes via the Nrf2 signalling pathway.

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.

Garlic bioactive substances and their therapeutic applications for improving human health: a comprehensive review.

Garlic (Allium sativum L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many in vitro and in vivo studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, ß-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and ß-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.

Allicin regulates Sestrin2 ubiquitination to affect macrophage autophagy and senescence, thus inhibiting the growth of hepatoma cells.

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 ß-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. CONCLUSION: Allicin can affect the autophagy of macrophages and restrain the growth of hepatoma cells by regulating the ubiquitination of Sestrin2.

Activity of propyl-propane-thiosulfinate and propyl-propane-thiosulfonate against carbapenem-resistant Gram-negative bacteria.

Organosulfur compounds derived from plants of the Allium genus, such as propyl-propane-thiosulfinate (PTS) and propyl-propane-thiosulfonate (PTSO), have been proposed as an alternative in antibiotic resistance. The aim of this study was to compare the activity of these substances with other antibiotics against clinical isolates of carbapenem-resistant (CAR-R) and carbapenem-susceptible (CAR-S) Gram-negative bacteria. A total of 126 clinical isolates of CAR-R and 155 CAR-S bacteria were selected, including Enterobacterales, A. baumannii and P. aeruginosa. The antibiotic susceptibility of all isolates was assessed using the microdilution and Kirby-Bauer methods for PTS, PTSO, amoxicillin/clavulanate, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, ciprofloxacin, and amikacin. Both PTS and PTSO demonstrated in vitro bactericidal activity against CAR-R Enterobacteriaceae and A. baumannii, with no significant difference in activity compared to their response against CAR-S isolates. However, both compounds were less active against P. aeruginosa than against any of the other bacteria, regardless of their resistance to carbapenems. In all cases, the minimum inhibitory concentration values of PTSO were significantly lower than those of PTS. These findings offer valuable information about the potential antibacterial use of these substances, particularly against infections that currently have limited therapeutic options.

Efficacy and safety of pyrotinib combined with albumin-bound paclitaxel as first-line treatment for HER2-positive metastatic breast cancer in patients previously treated with adjuvant and/or neoadjuvant trastuzumab therapy: The stage 1 results of a single-arm, phase 2 prospective clinical trial.

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

Thiosulfinate Tolerance Gene Clusters Are Common Features of Burkholderia Onion Pathogens.

Burkholderia gladioli pv. alliicola, B. cepacia, and B. orbicola are common bacterial pathogens of onion. Onions produce organosulfur thiosulfinate defensive compounds after cellular decompartmentalization. Using whole-genome sequencing and in silico analysis, we identified putative thiosulfinate tolerance gene (TTG) clusters in multiple onion-associated Burkholderia species similar to those characterized in other Allium-associated bacterial endophytes and pathogens. Sequence analysis revealed the presence of three Burkholderia TTG cluster types, with both Type A and Type B being broadly distributed in B. gladioli, B. cepacia, and B. orbicola in both the chromosome and plasmids. Based on isolate natural variation and generation of isogenic strains, we determined the in vitro and in vivo contribution of TTG clusters in B. gladioli, B. cepacia, and B. orbicola. The Burkholderia TTG clusters contributed to enhanced allicin tolerance and improved growth in filtered onion extracts by all three species. TTG clusters also made clear contributions to B. gladioli foliar necrosis symptoms and bacterial populations. Surprisingly, the TTG cluster did not contribute to bacterial populations in onion bulb scales by these three species. Based on our findings, we hypothesize onion-associated Burkholderia may evade or inhibit the production of thiosulfinates in onion bulb tissues. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Allicin Overcomes Doxorubicin Resistance of Breast Cancer Cells by Targeting the Nrf2 Pathway.

Breast cancer (BC) is a lethal disorder that threatens the life safety of the majority of females globally, with rising morbidity and mortality year by year. Doxorubicin is a cytotoxic anthracycline antibiotic that is widely used as one of the first-line chemotherapy agents for patients with BC. However, the efficacy of doxorubicin in the clinic is largely limited by its serious side effects and acquired drug resistance. Allicin (diallyl thiosulfinate), as the major component and key active compound present in freshly crushed garlic, has shown potential effects in suppressing chemotherapy resistance in various cancers. Our research aimed to explore the relationship between allicin and doxorubicin resistance in BC. To generate doxorubicin-resistant BC cell lines (MCF-7/DOX and MDA-MB-231/DOX), doxorubicin-sensitive parental cell lines MCF-7 and MDA-MB-231 were continuously exposed to stepwise increased concentrations of doxorubicin over a period of 6 months. CCK-8, colony formation, flow cytometry, RT-qPCR, and western blotting assays were performed to investigate the effects of allicin and/or doxorubicin treatment on the viability, proliferation and apoptosis and the expression of Nrf2, HO-1, phosphate AKT and AKT in doxorubicin-resistant BC cells. Our results showed that combined treatment of allicin with doxorubicin exhibited better effects on inhibiting the proliferation and enhancing the apoptosis of doxorubicin-resistant BC cells than treatment with allicin or doxorubicin alone. Mechanistically, allicin suppressed the levels of Nrf2, HO-1, and phosphate AKT in doxorubicin-resistant BC cells. Collectively, allicin improves the doxorubicin sensitivity of BC cells by inactivating the Nrf2/HO-1 signaling pathway.

Revitalizing allicin for cancer therapy: advances in formulation strategies to enhance bioavailability, stability, and clinical efficacy.

The main objective of this review is to highlight the therapeutic potential of allicin, a defense molecule in garlic known for its diverse health benefits, and address the key challenges of its bioavailability and stability. The research further aims to evaluate various formulation strategies and nanotechnology-based delivery systems that can resolve these issues and improve allicin's clinical efficacy, especially in cancer therapy. We conducted a comprehensive review of the available literature and previous studies, focusing on the therapeutic properties of allicin, its bioavailability, stability issues, and novel formulation strategies. We assessed the mechanism of action of allicin in cancer, including its effects on signaling pathways, cell cycle, apoptosis, autophagy, and tumor development. We also evaluated the outcomes of both in vitro and in vivo studies on different types of cancers, such as breast, cervical, colon, lung, and gastric cancer. Despite allicin's significant therapeutic benefits, including cardiovascular, antihypertensive, cholesterol-lowering, antimicrobial, antifungal, anticancer, and immune-modulatory activity, its clinical utility is limited due to poor stability and unpredictable bioavailability. Allicin's bioavailability in the gastrointestinal tract is dependent on the activity of the enzyme alliinase, and its stability can be affected by various conditions like gastric acid and intestinal enzyme proteases. Recent advances in formulation strategies and nanotechnology-based drug delivery systems show promise in addressing these challenges, potentially improving allicin's solubility, stability, and bioavailability. Allicin offers substantial potential for cancer therapy, yet its application is hindered by its instability and poor bioavailability. Novel formulation strategies and nanotechnology-based delivery systems can significantly overcome these limitations, enhancing the therapeutic efficacy of allicin. Future research should focus on refining these formulation strategies and delivery systems, ensuring the safety and efficacy of these new allicin formulations. Clinical trials and long-term studies should be carried out to determine the optimal dosage, assess potential side effects, and evaluate their real-world applicability. The comparative analysis of different drug delivery approaches and the development of targeted delivery systems can also provide further insight into enhancing the therapeutic potential of allicin.

Combating Black Fungus: Using Allicin as a Potent Antifungal Agent against Mucorales.

Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC50) of allicin was 25-72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin's promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections.

Allicin Alleviates Mitochondrial Dysfunction in Acrylamide-Induced Rat Kidney Involving the Regulation of SIRT1.

Acrylamide (AA), commonly formed in carbohydrate-rich thermally processed foods, exerts harmful effects on the kidney. Allicin, from crushed garlic cloves, exhibits strong biological activities. In the current study, the protection mechanisms of allicin against AA-caused nephrotoxicity were comprehensively examined using an in vivo rat model based on previous research that allicin plays a key role in improving renal function. The results showed that allicin attenuated histological changes of the kidney and ameliorated renal function. Damaged mitochondrial structures, upregulated voltage-dependent anion channel 1 expression, and decreased membrane potential and adenosine 5'-triphosphate levels were observed after AA treatment. Surprisingly, allicin notably reversed the adverse effects. Further, allicin effectively restored mitochondrial function via modulating mitochondrial biogenesis and dynamics, which might be associated with the upregulated expression of sirtuin 1 (SIRT1). Meanwhile, allicin dramatically activated the SIRT1 activity and subsequently inhibited p53 acetylation, prevented the translocation of cytochrome c to the cytoplasm, and reduced the caspase expression, thus further inhibiting mitochondrial apoptosis caused by AA. In summary, the relieving effect of allicin on AA-caused nephrotoxicity lies in its inhibition of mitochondrial dysfunction and mitochondrial apoptosis.

[Advances in cardiovascular protection effects and mechanisms of allicin].

Cardiovascular diseases(CVD) with high morbidity and mortality pose severe threats to human life. Allicin, a main active ingredient of garlic, possesses multiple pharmaceutical activities. It not only exerts cardioprotective effects but also prevents the risk factors for CVD. Allicin exerts cardioprotective effects via a variety of mechanisms, including inhibiting oxidative stress, apoptosis, autophagy, and inflammatory responses, regulating lipid metabolism and gut microbiota, inducing hydrogen sulfide production, and dilating vessels. Despite the valuable cardioprotective effects, the instability of allicin has hindered the basic research and clinical application. This paper reviews the progress in the cardioprotective effects and mechanisms of allicin in the last decade and summarizes the methods to improve the stability of allicin. In addition, this review provides a reference for further research and development of allicin in cardiovascular protection.

Current studies and potential future research directions on biological effects and related mechanisms of allicin.

Allicin, a thiosulfonate extract from freshly minced garlic, has been reported to have various biological effects on different organs and systems of animals and human. It can reduce oxidative stress, inhibit inflammatory response, resist pathogen infection and regulate intestinal flora. In addition, dozens of studies also demonstrated allicin could reduce blood glucose level, protect cardiovascular system and nervous system, and fight against cancers. Allicin was widely used in disease prevention and health care. However, more investigations on human cohort study are needed to verify the biological or clinical effects of allicin in the future. In this review, we summarized the biological effects of allicin from previous outstanding and valuable studies and provided useful information for future studies on the health effects of allicin.

Natural Compound Allicin Containing Thiosulfinate Moieties as Transmembrane Protein 16A (TMEM16A) Ion Channel Inhibitor for Food Adjuvant Therapy of Lung Cancer.

Cancer is one of the most serious malignant diseases, and chemotherapy is cancer's main clinical treatment method. However, chemotherapy inevitably produces drug resistance, and side effects accompany them. Adjuvant therapy is an effective way to enhance chemotherapeutic drug sensitivity and reduce side effects. This study found allicin, garlic's active ingredient, is an inhibitor of transmembrane protein 16A (TMEM16A), a novel drug target of lung adenocarcinoma. Allicin concentration-dependently inhibited TMEM16A currents with an IC50 of 24.35 ± 4.14 µM. Allicin thiosulfinate moieties bound with R535A/E624A/E633A residues of TMEM16A blocked the ion transport function and downregulated TMEM16A protein expression affecting the mitogen-activated protein kinase signal transduction. Then, allicin reduced the viability and migration of LA795 cells, and induced cell apoptosis. Moreover, multitarget combination administration results indicated that the therapeutic effect of 3.56 mg/kg allicin and 3 mg/kg cisplatin combined administration was superior to the superposition of the two drugs alone, demonstrating that the anticancer effects of allicin and cisplatin were synergistic. In addition, low-concentration combined administration also avoided the side effects of cisplatin in mice. Based on the good tumor suppressor effect and high biosafety of allicin and cisplatin combination in vivo, allicin can be used for food adjuvant therapy of cisplatin chemotherapy.