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Metabolic syndrome is a common metabolic disorder which has become a public health challenge worldwide. There has been growing interest in medications including natural products as complementary or alternative choices for common chemical therapeutics regarding their limited side effects and ease of access. Nanosizing these compounds may help to increase their solubility, bioavailability, and promisingly enhance their efficacy. This study, for the first time, provides a comprehensive overview of the application of natural-products-based nanoformulations in the management of metabolic syndrome. Different phytochemicals including curcumin, berberine, Capsicum oleoresin, naringenin, emodin, gymnemic acid, resveratrol, quercetin, scutellarin, stevioside, silybin, baicalin, and others have been nanosized hitherto, and their nanosizing method and effect in treatment and alleviating metabolic syndrome have been reviewed and discussed in this study. It has been discovered that there are several pathways or molecular targets relevant to metabolic disorders which are affected by these compounds. Various natural-based nanoformulations have shown promising effect in treatment of metabolic syndrome, and therefore can be considered as future candidates instead of or in conjunction with pharmaceutical drugs if they pass clinical trials successfully.

Considering the high prevalence of cardiovascular diseases (CVDs), the primary cause of death during the last several decades, it is necessary to develop proper strategies for the prevention and treatment of CVDs. Given the excessive side effects of current therapies, alternative therapeutic approaches like medicinal plants and natural products are preferred. Lower toxicity, chemical diversity, cost-effectiveness, and proven therapeutic potentials make natural products superior compared to other products. Nanoformulation methods improve the solubility, bioavailability, circulation time, surface area-to-volume ratio, systemic adverse side effects, and drug delivery efficiency of these medications. This study intended to review the functionality of the most recent nanoformulated medicinal plants and/or natural products against various cardiovascular conditions such as hypertension, atherosclerosis, thrombosis, and myocardial infarction. Literature review revealed that curcumin, quercetin, and resveratrol were the most applied natural products, respectively. Combination therapy, conjugation, or fabrication of nanoparticles and nanocarriers improved the applications and therapeutic efficacy of herbal- or natural-based nanoformulations. In the context of CVDs prevention and/or treatment, available data suggest that natural-based nanoformulations are considerably efficient, alone or in blend with other herbal/synthetic medicines. However, clinical trials are mandatory to elucidate the safety, cardioprotective effect, and mechanism of actions of nanophytomedicines.

Doxorubicin (DOX) is commonly used for the treatment of various types of cancer, however can cause serious side effects, including cardiotoxicity. The mechanisms involved in DOX-induced cardiac damage are complex and not yet fully understood. One mechanism is the disruption of cardiac metabolism, which can impair cardiac function. The mammalian target of rapamycin (mTOR) is a key regulator of cardiac energy metabolism, and dysregulation of mTOR signaling has been implicated in DOX-induced cardiac dysfunction. Natural compounds (NCs) have been shown to improve cardiac function in vivo and in vitro models of DOX-induced cardiotoxicity. This review article explores the protective effects of NCs against DOX-induced cardiac injury, with a focus on their regulation of mTOR signaling pathways. Generally, the modulation of mTOR signaling by NCs represents a promising strategy for decreasing the cardiotoxic effects of DOX.

Cisplatin is a widely used chemotherapeutic agent for the treatment of various cancers. However, the clinical use of cisplatin is limited by its cardiotoxic side effects. The primary mechanisms implicated in this cardiotoxicity include mitochondrial dysfunction, oxidative stress, inflammation, and apoptotic. Numerous natural compounds (NCs) have been introduced as promising protective factors against cisplatin-mediated cardiac damage. The current review summarized the potential of various NCs as cardioprotective agents at the molecular levels. These compounds exhibited potent antioxidant and anti-inflammatory effects by interaction with the PI3K/AKT, AMPK, Nrf2, NF-κB, and NLRP3/caspase-1/GSDMD pathways. Generally, the modulation of these signaling pathways by NCs represents a promising strategy for improving the therapeutic index of cisplatin by reducing its cardiac side effects.

Aging is known as a main risk factor in the development of cardiovascular diseases. Naringin (NRG) is a flavonoid compound derived from citrus fruits. It possesses a wide spectrum of pharmacological properties, including antioxidant anti-inflammatory, and cardioprotective. This investigation aimed to assess the cardioprotective effect of NRG against the ischemia/reperfusion (I/R) injury in aged rats. In this study, D-galactose (D-GAL) at the dose of 150 mg/kg/day for 8 weeks was used to induce aging in rats. Rats were orally gavaged with NRG (40 or 100 mg/kg/day), in co-treatment with D-GAL, for 8 weeks. The Langendorff isolated heart was used to evaluate the effect of NRG on I/R injury in aged rats. NRG treatment diminished myocardial hypertrophy and maximum contracture level in aged animals. During the pre-ischemic phase, reduced heart rate was normalized by NRG. The effects of D-GAL on the left ventricular end diastolic pressure (LVDP), the rate pressure product (RPP), and the minimum and maximum rate of left ventricular pressure (±dp/dt) improved by NRG treatment in the perfusion period. NRG also enhanced post-ischemic recovery of cardiac functional parameters (± dp/dt, and RPP) in isolated hearts. An increase in serum levels of the lactate dehydrogenase (LDH), the creatine kinase-MB (CK-MB), and the tumor necrosis factor-alpha (TNF-α) were reversed by NRG in aged rats. It also normalized the D-GAL-decreased the superoxide dismutase (SOD) activity in the heart tissue. NRG treatment alleviated cardiac injury in aged hearts under conditions of I/R. NRG may improve aging-induced cardiac dysfunction through anti-oxidative and anti-inflammatory mechanisms.

Doxorubicin (DOX) is a chemotherapy drug known to induce metabolic changes in the heart, leading to potential heart toxicity. These changes impact various cellular functions and pathways such as disrupting the mechanistic target of rapamycin (mTOR) signaling pathway. The study aimed to investigate the effect of DOX on the mTOR pathway through an in vivo systematic review. Databases were searched on September 11, 2023. We finally included 30 in vivo studies that examined the mTOR expression in cardiac tissue samples. The present study has shown that the PI3K/AKT/mTOR, the AMPK/mTOR, the p53/mTOR signaling, the mTOR/TFEB pathway, the p38 MAPK/mTOR, the sestrins/mTOR, and the KLF15/eNOS/mTORC1 signaling pathways play a crucial role in the development of DOX-induced cardiotoxicity. Inhibition or dysregulation of these pathways can lead to increased oxidative stress, apoptosis, and other adverse effects on the heart. Strategies that target and modulate the mTOR pathways, such as the use of mTOR inhibitors like rapamycin, have the potential to enhance the anticancer effects of DOX while also mitigating its cardiotoxic side effects.

Doxorubicin (DOX) induces cardiac dysfunction. Paracetamol (APAP) has also been established as an effective cardioprotective agent during ischemia/reperfusion. Therefore, this study aims to evaluate the effect of APAP on DOX-induced cardiotoxicity in ischemia/reperfused isolated rat heart. A total of 36 rats were equally divided into four groups: control, DOX (30 min, 20 µM DOX perfusion), APAP (15 min before and after ischemia, 0.35 mM APAP perfusion), and DOX+APAP (perfused with the same protocol in DOX and APAP groups). The isolated hearts were perfused according to the Langendorff method. Cardiac parameters, including left ventricular developed pressure (LVDP), heart rate (HR), coronary flow (CF), and rate pressure product (RPP; LVDP×HR) were measured. Lactate dehydrogenase (LDH) concentration was also assessed. At the end of the baseline period, the RPP, HR, and CF values were lower in the DOX group than in the control group (p<0.01). Meanwhile, there were no significant differences between the values of cardiac function parameters in the DOX+APAP and control groups. In the reperfusion period, the RPP and CF values were significantly increased in the DOX+APAP group compared with the DOX group (p<0.05). Furthermore, the LDH concentration was decreased in the DOX+APAP group compared with the DOX group. APAP perfusion protected the hearts against DOX-induced cardiotoxicity in the baseline and ischemia/reperfusion conditions. These findings can be explained by the effect of APAP on antioxidant capacity and mitochondrial permeability transition pores.

Allium hirtifolium (Persian shallot) has a hypoglycemic effect on diabetic animals. The aim of this study was to assess the effect of the ethyl acetate fraction of Allium hirtifolium on the function of isolated hearts of diabetic rats. The control and diabetic animals were randomly divided into four groups: saline- or extract-treated controls (n=10 and n=6, respectively) and saline- or extract-treated diabetic rats (n=8 and n=9, respectively), which received normal saline or extract for four weeks by daily gavage. The hearts were perfused according to the Langendorff method. Cardiac function parameters, including left ventricular developed pressure (LVDP), heart rate (HR), rate pressure product (RPP; LVDP×HR), and dp/dt were measured. The findings of this study showed that in the extract-treated diabetic rats, LVDP (94.5±9.1 mm Hg, mean±SEM), HR (249±15 beats/min), RPP (22732±1246) and +dp/dt (2598±230) at the baseline were significantly higher than those in the saline-treated diabetic animals, (71.5±4.0), (189±6), (13923±984), and (1701±124), respectively. Furthermore, RPP and HR were also significantly higher than the corresponding values obtained in the saline-treated diabetic rats after ischemia. Besides blood glucose lowering action, oral administration of the ethyl acetate fraction of Allium hirtifolium significantly improved the baseline and post-ischemic cardiac function parameters in streptozotocin-induced diabetic rats.