Nanophytomedicines for the Prevention of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review.

Metabolic syndrome includes a series of metabolic abnormalities that leads to diabetes mellitus and cardiovascular diseases. Plant extracts, due to their unique advantages like anti-inflammatory, antioxidant, and insulin sensitizing properties, are interesting therapeutic options to manage MetS; however, the poor solubility and low bioavailability of lipophilic bioactive components in the herbal extracts are two critical challenges. Nano-scale delivery systems are suitable to improve delivery of herbal extracts. This review, for the first time, focuses on nanoformulations of herbal extracts in MetS and related complications. Included studies showed that several forms of nano drug delivery systems such as nanoemulsions, solid lipid nanoparticles, nanobiocomposites, and green-synthesized silver, gold, and zinc oxide nanoparticles have been developed using herbal extracts. It was shown that the method of preparation and related parameters such as temperature and type of polymer are important factors affecting physicochemical stability and therapeutic activity of the final product. Many of these formulations could successfully decrease the lipid profile, inflammation, oxidative damage, and insulin resistance in in vitro and in vivo models of MetS-related complications. Further studies are still needed to confirm the safety and efficacy of these novel herbal formulations for clinical application.

Evaluation of the Cytotoxic and Apoptogenic Effects of Glabridin and Its Effect on Cytotoxicity and Apoptosis Induced by Doxorubicin Toward Cancerous Cells.

Purposes: In the present study, we tried for the first time to examine the anti-proliferative and anti-apoptogenic effect of Glabridin (Glab) toward three groups of cancer cells (SKNMC, H1299, and A2780). Furthermore, the possibility of co-administration of Glab with doxorubicin (DOX) to these cells was also examined to find out whether Glab can potentiate the cytotoxic effect of this chemotherapy agent. Methods: Different cellular assays (MTT, caspase-3 activity, MMP, RT-PCR analysis) were carried out on the cancer cells treated with Glab. Results: Cellular toxicity assay revealed that Glab can potentially reduce the viability of these cells with IC50 concentrations up to 10, 12, and 38 µM toward A2780, SKNMC, and H1299 cell lines, respectively. The results of MMP and caspase-3 activity assays, in association with the results corresponding to the BAX and Bcl-2 gene expressions, altogether revealed that Glab can exert apoptogenic effect on these cells. The intrinsic mitochondrial pathway was found to be the main mechanism, in which Glab induced apoptosis toward H1299 cells and SKNMC cells, while the apoptosis mechanism for A2780 cells could be probably through extrinsic pathway. Glab also potentiated the cytotoxic effect of DOX and its accumulation in H1299 cell line. Conclusion: The results of this study revealed the promising cytotoxic role of Glab on different carcinoma cells. These data also suggested that co-chemotherapy method using Glab could be effective for treatment of cancer, but further in-vivo and clinical studies are still needed to assure these results.

Nanoformulations of natural products for management of metabolic syndrome.

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.

Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence.

Neuroprotection is the preservation of function and networks of neural tissues from damages caused by various agents, as well as neurodegenerative diseases such as Parkinson's, Alzheimer's, Huntington's diseases, and multiple sclerosis. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against development of neurodegenerative diseases. Our review discusses neuropharmacological mechanisms for preventive and therapeutic effects of hesperidin in neurodegenerative diseases. In addition, the review examines clinical evidence confirming its neuroprotective function. Various cellular and animal models specific to neurodegenerative diseases have been conducted to evaluate the underlying neuropharmacological mechanisms of hesperidin. Neuroprotective potential of this flavonoid is mediated by improvement of neural growth factors and endogenous antioxidant defense functions, diminishing neuro-inflammatory and apoptotic pathways. Despite the various preclinical studies on the role of hesperidin in the neurodegenerative diseases, less is known about its definite effect on humans. A limited number of clinical trials showed that hesperidin-enriched dietary supplements can significantly improve cerebral blood flow, cognition, and memory performance. Further clinical trials are also required for confirming neuroprotective efficacy of this natural flavonoid and evaluating its safety profile.

Acute and Subchronic Toxicological Evaluations of Allium rotundum L.: A Dietary Plant from Iran.

Allium rotundum L. is a dietary plant with diverse nutritional and herbal applications. According to its widespread application in Iranians' diets, understanding the possible adverse effects and toxic activities could be of major importance. The aim of this study was to establish the acute and subchronic toxicity profile of the hydroalcoholic extract of Allium rotundum on male and female Wistar rats. The acute study indicated no adverse effect or toxic activity after administration of the extract, suggesting that the LD50 value is up to 5,000 mg/kg body weight for the extract. The subchronic study at three doses (250, 500, and 750 mg/kg body weight/day) supported the results of acute study and revealed that no abnormal change or toxicity was induced by the extract in both male and female Wistar rats. All the biochemical and hematological parameters of the treated rats were in historical range after long-term administration of the extract. The histopathological examination also revealed no lesion or alteration in the tissue of vital organs (kidney, liver, heart, lung, and spleen). The NOAEL (no observed adverse effect level) value was high enough (greater than 750 mg/kg body weight/ day) to conclude the nontoxic nature of this extract. The safety of this extract was affirmed by the acute and subchronic toxic studies and suggested that this plant could be a proper and effective dietary plant due to its high nutritive value and inherent therapeutic properties.

Natural product-based nanomedicines for wound healing purposes: therapeutic targets and drug delivery systems.

Wound healing process is an intricate sequence of well-orchestrated biochemical and cellular phenomena to restore the integrity of the skin and subcutaneous tissue. Several plant extracts and their phytoconstituents are known as a promising alternative for wound healing agents due to the presence of diverse active components, ease of access, and their limited side effects. The development of nanotechnological methods can help to improve the efficacy of different therapeutics as well as herbal-based products. Here, we present a review of the efficacy of the plant based-nanomaterials in the management of wounds and discuss the involved therapeutic targets. For this purpose, a profound search has been conducted on in vitro, in vivo, and/or clinical evidences evaluating the efficacy and pharmacological mechanisms of natural product-based nanostructures on different types of wounds. Different pharmacological targets are involved in the wound healing effects of herbal-based nanostructures, including suppressing the production of inflammatory cytokines and inflammatory transduction cascades, reducing oxidative factors and enhancing antioxidative enzymes, and promoting neovascularization and angiogenic pathways through increasing the expression of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor. Moreover, nanostructure of plant extracts and their phytochemicals can enhance their bioavailability, control their release in the form of sustained delivery systems to the wound site, and enhance the permeability of these therapeutics to the underlying skin layers, which are all necessary for the healing process. Overall, various plant extracts and their natural compounds, used in nanoformulations, have demonstrated high activity in the management of wounds and thus can be assumed as future pharmaceutical drugs.

Dietary Plants for the Prevention and Management of Kidney Stones: Preclinical and Clinical Evidence and Molecular Mechanisms.

Kidney stones are one of the oldest known and common diseases in the urinary tract system. Various human studies have suggested that diets with a higher intake of vegetables and fruits play a role in the prevention of kidney stones. In this review, we have provided an overview of these dietary plants, their main chemical constituents, and their possible mechanisms of action. Camellia sinensis (green tea), Rubus idaeus (raspberry), Rubia cordifolia (common madder), Petroselinum crispum (parsley), Punica granatum (pomegranate), Pistacia lentiscus (mastic), Solanum xanthocarpum (yellow-fruit nightshade), Urtica dioica (stinging nettle), Dolichos biflorus (horse gram), Ammi visnaga (khella), Nigella sativa (black-cumin), Hibiscus sabdariffa (roselle), and Origanum vulgare (oregano) have received considerable interest based on scientific evidence. Beside these dietary plants, phytochemicals-such as catechin, epicatechin, epigallocatechin-3-gallate, diosmin, rutin, quercetin, hyperoside, and curcumin-as antioxidant dietary phyto-phenols were found to be effective for the prevention of urolithiasis (the process of stone formation in the urinary tract). The main underlying mechanisms of these dietary plants and their isolated phytonutrients in the management of urolithiasis include diuretic, antispasmodic, and antioxidant activity, as well as an inhibitory effect on crystallization, nucleation, and aggregation of crystals. The results as presented in this review demonstrate the promising role of dietary plants and phytophenols in the prevention and management of kidney stones. Further investigations are required to confirm the safety and efficacy of these compounds.