Citrus flavonoids and adhesion molecules: Potential role in the management of atherosclerosis.

Atherosclerosis as a chronic inflammatory disorder is accompanied with oxidative stress which causes a high morbidity and mortality. Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and E-selectin, are amongst the most important contributors in atherosclerosis. In such cases, dietary interventions with functional foods containing natural antioxidant and anti-inflammatory constituents are of a great interest. Citrus fruits are rich sources of flavonoids as natural pigments with potent antioxidant and anti-inflammatory activities. This study aims to review current evidence regarding the role of citrus flavonoids in the management of atherosclerosis with a focus on their effect on adhesion molecules. Electronic databases including PubMed, Scopus, and Web of Science were searched with the names of adhesion molecules and flavonoids from inception until January 2023. The included articles highly support the beneficial effects of citrus flavonoids in preclinical models of atherosclerosis. Quercetin, naringin and naringenin, hesperidin and hesperetin, nobiletin, rutin, luteolin, apigenin, and kaempferol are the most common flavonoids in citrus fruits which could modulate adhesion molecules including ICAM-1, VCAM-1, E-selectin, and P-selectin. Additionally, markers of chronic inflammation such as interleukins, tumor necrosis factor-α, nuclear factor-κB, and nitric oxide signaling, as well as oxidative stress markers like superoxide dismutase and glutathione were all normalized upon administration of citrus flavonoids. Conclusively, this review confirms the modulatory role of flavonoids on adhesion molecules in atherosclerosis based on the preclinical evaluations. Thus, citrus fruits can be further studied in atherosclerotic patients regarding their activity in reducing adhesion molecules.

In-vitro and in-vivo evaluation of chitosan-based thermosensitive gel containing lorazepam NLCs for the treatment of status epilepticus.

The objective of this study was to develop an in-situ gel containing lorazepam (LZM) loaded nanostructured lipid carriers (NLCs) for direct nose-to-brain delivery in order to increase drug therapeutic efficacy in the treatment of epilepsy. Accordingly, LZM loaded NLCs were formulated using emulsification solvent diffusion and evaporation method; then the effects of the formulation variables on different physicochemical characteristics of NLCs were investigated. Thermosensitive in-situ gels containing LZM-NLCs were prepared using a combination of chitosan and ß-glycerol phosphate (ß-GP). The anticonvulsant efficacy of LZM-NLCs-Gel was then examined using the pentylenetetrazole (PTZ) model. The optimised NLCs were spherical, showing the particle size of 71.70 ± 5.16 nm and the zeta potential of -20.06 ± 2.70 mV. The pH and gelation time for the chitosan solution with 15% (w/v) ß-GP were determined to be 7.12 ± 0.03 and 5.33 ± 0.58 min, respectively. The in-vivo findings showed that compared with the control group and the group that received LZM-Gel, the occurrence of PTZ-induced seizures in the rats was significantly reduced by LZM-NLCs-Gel after intranasal administration. These results, therefore, suggested that the LZM-NLCs-Gel system could have potential applications for brain targeting through nasal route and might increase LZM therapeutic efficacy in the treatment of epilepsy.

Effect of L. acidophilus and B. lactis on blood glucose in women with gestational diabetes mellitus: a randomized placebo-controlled trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is a complication of pregnancy that can be associated with neonatal complications and adverse pregnancy outcomes. Recently, probiotic use has been proposed for better control of glucose in GDM patients. The aim of this study was to evaluate the effect of probiotic yoghurt compare with ordinary yoghurt on GDM women. METHODS: In this double-blind placebo-controlled clinical trial, 84 pregnant women with GDM were randomly assigned into two groups of 42 recipients who underwent 300 g/day of probiotic yoghurt or placebo for 8 weeks. Blood glucose, HbA1c, and the outcome of pregnancy were compared between the two groups after the intervention. RESULTS: According to the findings of present trial no significant differences were observed in general characteristics between the two groups (p > 0.05). Both fasting and post prandial blood glucose as well as the level of HbA1c were decreased significantly in probiotic group (p < 0.05), although these changes are not statistically significant in the placebo group. The between group differences was significant after the 2 month intervention (p < 0.05). Neonates born of probiotic group mothers, have significantly lower weight and fewer macrosome neonates were born in this group compared with control group (p < 0.05). However, no difference was observed in other values of outcome. CONCLUSIONS: Our study revealed that better control of blood glucose can be achieved by consumption of probiotic yoghurt in patients whose pregnancy is complicated by GDM, compared with placebo. Also incidence of macrosomia may be decreased by this regimen.

Polyphenols for diabetes associated neuropathy: Pharmacological targets and clinical perspective.

OBJECTIVES: Diabetic neuropathy (DNP) is a widespread and debilitating complication with complex pathophysiology that is caused by neuronal dysfunction in diabetic patients. Conventional therapeutics for DNP are quite challenging due to their serious adverse effects. Hence, there is a need to investigate novel effective and safe options. The novelty of the present study was to provide available therapeutic approaches, emerging molecular mechanisms, signaling pathways and future directions of DNP as well as polyphenols' effect, which accordingly, give new insights for paving the way for novel treatments in DNP. EVIDENCE ACQUISITION: A comprehensive review was done in electronic databases including Medline, PubMed, Web of Science, Scopus, national database (Irandoc and SID), and related articles regarding metabolic pathways on the pathogenesis of DNP as well as the polyphenols' effect. The keywords "diabetic neuropathy" and "diabetes mellitus" in the title/abstract and "polyphenol" in the whole text were used. Data were collected from inception until May 2019. RESULTS: DNP complications is mostly related to a poor glycemic control and metabolic imbalances mainly inflammation and oxidative stress. Several signaling and molecular pathways play key roles in the pathogenesis and progression of DNP. Among natural entities, polyphenols are suggested as multi-target alternatives affecting most of these pathogenesis mechanisms in DNP. CONCLUSION: The findings revealed novel pathogenicity signaling pathways of DNP and affirmed the auspicious role of polyphenols to tackle these destructive pathways in order to prevent, manage, and treat various diseases. Graphical Abstract .

Medicinal plants and their isolated phytochemicals for the management of chemotherapy-induced neuropathy: therapeutic targets and clinical perspective.

BACKGROUND: Chemotherapy, as one of the main approaches of cancer treatment, is accompanied with several adverse effects, including chemotherapy-induced peripheral neuropathy (CIPN). Since current methods to control the condition are not completely effective, new treatment options should be introduced. Medicinal plants can be suitable candidates to be assessed regarding their effects in CIPN. Current paper reviews the available preclinical and clinical studies on the efficacy of herbal medicines in CIPN. METHODS: Electronic databases including PubMed, Scopus, and Cochrane library were searched with the keywords "neuropathy" in the title/abstract and "plant", "extract", or "herb" in the whole text. Data were collected from inception until April 2018. RESULTS: Plants such as chamomile (Matricaria chamomilla L.), sage (Salvia officinalis L.), cinnamon (Cinnamomum cassia (L.) D. Don), and sweet flag (Acorus calamus L.) as well as phytochemicals like matrine, curcumin, and thioctic acid have demonstrated beneficial effects in animal models of CIPN via prevention of axonal degeneration, decrease in total calcium level, improvement of endogenous antioxidant defense mechanisms such as superoxide dismutase and reduced glutathione, and regulation of neural cell apoptosis, nuclear factor-ĸB, cyclooxygenase-2, and nitric oxide signaling. Also, five clinical trials have evaluated the effect of herbal products in patients with CIPN. CONCLUSIONS: There are currently limited clinical evidence on medicinal plants for CIPN which shows the necessity of future mechanistic studies, as well as well-designed clinical trial for further confirmation of the safety and efficacy of herbal medicines in CIPN. Graphical abstract Schematic mechanisms of medicinal plants to prevent chemotherapy-induced neuropathy: NO: nitric oxide, TNF: tumor necrosis factor, PG: prostaglandin, NF-ĸB: nuclear factor kappa B, LPO: lipid peroxidation, ROS: reactive oxygen species, COX: cyclooxygenase, IL: interleukin, ERK: extracellular signal-related kinase, X: inhibition, ↓: induction.

Plant-derived medicines for neuropathies: a comprehensive review of clinical evidence.

Neuropathy is defined as the damage to the peripheral or central nervous system accompanied by pain, numbness, or muscle weakness, which can be due to congenital diseases or environmental factors such as diabetes, trauma, or viral infections. As current treatments are not sufficiently able to control the disease, studies focusing on the identification and discovery of new therapeutic agents are necessary. Natural products have been used for a long time for the management of different neurological problems including neuropathies. The aim of the present study is to review the current clinical data on the beneficial effects of medicinal plants in neuropathy. Electronic databases including PubMed, Scopus, and Cochrane Library were searched with the keywords 'neuropathy' in the title/abstract and 'plant' or 'extract' or 'herb' in the whole text from inception until August 2017. From a total of 3679 papers, 22 studies were finally included. Medicinal plants were evaluated clinically in several types of neuropathy, including diabetic neuropathy, chemotherapy-induced peripheral neuropathy, carpal tunnel syndrome, and HIV-associated neuropathy. Some studies reported the improvement in pain, nerve function, nerve conduction velocity, and quality of life. Cannabis sativa (hemp), Linum usitatissimum (linseed oil), capsaicin, and a polyherbal Japanese formulation called Goshajinkigan had the most evidence regarding their clinical efficacy. Other investigated herbal medicines in neuropathy, such as Matricaria chamomilla (chamomile), Curcuma longa (turmeric), and Citrullus colocynthis (colocynth), had only one clinical trial. Thus, future studies are necessary to confirm the safety and efficacy of such natural medicines as a complementary or alternative treatment for neuropathy.

Dietary polyphenols for atherosclerosis: A comprehensive review and future perspectives.

Atherosclerosis is one of the most prevalent reasons for premature death in adults. Despite the several conventional drugs in the market; many patients are not completely treated. Here we comprehensively review current clinical evidence regarding the efficacy of dietary polyphenols in atherosclerosis and related complications. PubMed, Cochrane library and Scopus were searched from inception until August 2016 to obtain clinical trials in which polyphenols were evaluated in cardiovascular parameters related to atherosclerosis. From total of 13031 results, 49 clinical trials were finally included. Tyrosol derivatives from virgin olive oil, catechins and theaflavins from green and black tea, cocoa polyphenols, and red grape resveratrol, as well as anthocyanins were the most studied polyphenolic compounds which could regulate lipid profile, inflammation and oxidative stress, blood pressure, endothelial function, and cell adhesion molecules. The most important limitations of the included trials were small sample size, short follow up, and unqualified methodology. Future well-designed clinical trials are necessary to provide better level of evidence for clinical decision making.