Allylmethylsulfide, a Sulfur Compound Derived from Garlic, Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats

Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on chronic administration and has a potential antihypertrophic effect. Chronic administration of AMS for 30 days did not cause any significant differences in the body weight, electrocardiogram, food intake, serum biochemical parameters, and histopathology of vital organs. Single-dose pharmacokinetics of AMS suggests that AMS is rapidly metabolized into Allylmethylsulfoxide (AMSO) and Allylmethylsulfone (AMSO2). To evaluate the efficacy of AMS, cardiac hypertrophy was induced by subcutaneous implantation of ALZET® osmotic minipump containing isoproterenol (~5 mg/kg/day), cotreated with AMS (25 and 50 mg/kg/day) and enalapril (10 mg/kg/day) for 2 weeks. AMS and enalapril significantly reduced cardiac hypertrophy as studied by the heart weight to body weight ratio and mRNA expression of fetal genes (ANP and β-MHC). We have observed that TBARS, a parameter of lipid peroxidation, was reduced and the antioxidant enzymes (glutathione, catalase, and superoxide dismutase) were improved in the AMS and enalapril-cotreated hypertrophic hearts. The extracellular matrix (ECM) components such as matrix metalloproteinases (MMP2 and MMP9) were significantly upregulated in the diseased hearts; however, with the AMS and enalapril, it was preserved. Similarly, caspases 3, 7, and 9 were upregulated in hypertrophic hearts, and with the AMS and enalapril treatment, they were reduced. Further to corroborate this finding with in vitro data, we have checked the nuclear expression of caspase 3/7 in the H9c2 cells treated with isoproterenol and observed that AMS cotreatment reduced it significantly. Histopathological investigation of myocardium suggests AMS and enalapril treatment reduced fibrosis in hypertrophied hearts. Based on our experimental results, we conclude that AMS, an active metabolite of garlic, could reduce isoproterenol-induced cardiac hypertrophy by reducing oxidative stress, apoptosis, and stabilizing ECM components

Sirt1 and Sirt3 Activation Improved Cardiac Function of Diabetic Rats via Modulation of Mitochondrial Function

In the present study, we aimed to evaluate the effect of Sirt1, Sirt3 and combined activation in high fructose diet-induced insulin resistance rat heart and assessed the cardiac function focusing on mitochondrial health and function. We administered the Sirt1 activator; SRT1720 (5 mg/kg, i.p.), Sirt3 activator; Oroxylin-A (10 mg/kg i.p.) and the combination; SRT1720 + Oroxylin-A (5 mg/kg and 10 mg/kg i.p.) daily from 12th week to 20th weeks of study. We observed significant perturbations of most of the cardiac structural and functional parameters in high fructose diet-fed animals. Administration of SRT1720 and Oroxylin-A improved perturbed cardiac structural and functional parameters by decreasing insulin resistance, oxidative stress, and improving mitochondrial function by enhancing mitochondrial biogenesis, OXPHOS expression and activity in high fructose diet-induced insulin-resistant rats. However, we could not observe the synergistic effect of SRT1720 and Oroxylin-A combination. Similar to in-vivo study, perturbed mitochondrial function and oxidative stress observed in insulin-resistant H9c2 cells were improved after activation of Sirt1 and Sirt3. We observed that Sirt1 activation enhances Sirt3 expression and mitochondrial biogenesis, and the opposite effects were observed after Sirt1 inhibition in cardiomyoblast cells. Taken together our results conclude that activation of Sirt1 alone could be a potential therapeutic target for diabetes-associated cardiovascular complications

Sirt1 and Sirt3 Activation Improved Cardiac Function of Diabetic Rats via Modulation of Mitochondrial Function

In the present study, we aimed to evaluate the effect of Sirt1, Sirt3 and combined activation in high fructose diet-induced insulin resistance rat heart and assessed the cardiac function focusing on mitochondrial health and function. We administered the Sirt1 activator; SRT1720 (5 mg/kg, i.p.), Sirt3 activator; Oroxylin-A (10 mg/kg i.p.) and the combination; SRT1720 + Oroxylin-A (5 mg/kg and 10 mg/kg i.p.) daily from 12th week to 20th weeks of study. We observed significant perturbations of most of the cardiac structural and functional parameters in high fructose diet-fed animals. Administration of SRT1720 and Oroxylin-A improved perturbed cardiac structural and functional parameters by decreasing insulin resistance, oxidative stress, and improving mitochondrial function by enhancing mitochondrial biogenesis, OXPHOS expression and activity in high fructose diet-induced insulin-resistant rats. However, we could not observe the synergistic effect of SRT1720 and Oroxylin-A combination. Similar to in-vivo study, perturbed mitochondrial function and oxidative stress observed in insulin-resistant H9c2 cells were improved after activation of Sirt1 and Sirt3. We observed that Sirt1 activation enhances Sirt3 expression and mitochondrial biogenesis, and the opposite effects were observed after Sirt1 inhibition in cardiomyoblast cells. Taken together our results conclude that activation of Sirt1 alone could be a potential therapeutic target for diabetes-associated cardiovascular complications

Allicin and health: A comprehensive review

Background: Allicin is an organosulfur and defensive compound found in garlic (Allium sativum L.) and other Allium species. Its unique odor is easily detectable, and its effects on human health have been studied since ancient times. Scope and approach: In this compressive review we report the presence of allicin in different Allium species, their biosynthesis, pharmacokinetics, absorption, and safety profile. Among the main allicin applications highlight its antimicrobial and antiparasitic properties, reviewed in the present work from in vitro evidence and in vivo studies. Finally, special attention was also given to the allicin state of the art in human health, including in vitro and in vivo assays, and clinical trials, on antioxidant, anticancer, antidiabetic and immunomodulatory effects, besides to its contribution as a cardioprotective agent. Key findings and conclusions: The promising capacity of allicin to interact with thiol groups seems to be directly related to its antimicrobial potential, showing both antibacterial and antifungal activities. Allicin also displayed an interesting potential in the prevention and treatment of several diseases including diabetes mellitus, cardiovascular disease, and cancer. Indeed, its antioxidant and immunomodulatory effects are some of the mechanisms that may explain their biological activities. Future applications should be directed to allicin pharmaceutical formulation, its delivery and its compatibility with food matrices and other drugs due to allicin biosynthesis, instability, reactivity, and volatility

Medicinal and mechanistic overview of artemisinin in the treatment of human diseases

Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral infections, bacterial infections, and some cardiovascular diseases, especially in Asia, North America, Europe and other parts of the world. This comprehensive review aims to update the biomedical potential of ART and its derivatives for treating human diseases highlighting its pharmacokinetic and pharmacological properties based on the results of experimental pharmacological studies in vitro and in vivo. Cellular and molecular mechanisms of action, tested doses and toxic effects of artemisinin were also described. The analysis of data based on an up-to-date literature search showed that ART and its derivatives display anticancer effects along with a wide range of pharmacological activities such as antibacterial, antiviral, antimalarial, antioxidant and cardioprotective effects. These compounds have great potential for discovering new drugs used as adjunctive therapies in cancer and various other diseases. Detailed translational and experimental studies are however needed to fully understand the pharmacological effects of these compounds