Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder and is characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Obesity, low-grade chronic inflammatory status, and insulin-resistance (IR) often coexist in PCOS. The Mediterranean diet (MD) is an anti-inflammatory dietary pattern, which is rich in complex carbohydrates and fiber, and high in monounsaturated fat. There is a close association among obesity, low-grade chronic inflammation, IR, and hormonal derangements in PCOS. The main aim of the present study was to evaluate the adherence to MD, the dietary intake, and the body composition and their association with PCOS clinical severity in a cohort of treatment-naïve women with PCOS when compared with a control group of healthy women matched for age and body mass index (BMI). In this case-controlled, cross-sectional study, we enrolled 112 patients with PCOS and 112 controls. PREvención con DIetaMEDiterránea (PREDIMED) and seven-day food records were used to evaluate the degree of adherence to the MD and dietary pattern, respectively. Body composition was evaluated by bioelectrical impedance analysis (BIA) phase-sensitive system. Testosterone levels and Ferriman-Gallwey score assessed the clinical severity of PCOS. C-reactive protein (CRP) levels were determined with a nephelometric assay with CardioPhase high sensitivity. PCOS women showed higher testosterone levels, Ferriman-Gallwey score, fasting insulin and glucose levels, and Homeostatic Model Assessment (HoMA)-IR when compared with the control group (p < 0.001). In addition, we found that the PCOS women consumed less extra-virgin olive oil, legumes, fish/seafood, and nuts compared with control group. Despite no differences in energy intake between the two groups, the PCOS women consumed a lower quantity of complex carbohydrate, fiber, monounsaturated fatty acids (MUFA), and n-3 polyunsaturated fatty acid (PUFA), and higher quantity of simple carbohydrate, total fat, saturated fatty acid (SFA), PUFA and n-6 PUFA than the control group. The PCOS women have an adverse body composition when compared with controls, with the lowest values of phase angle (PhA) and fat-free mass (p < 0.001). Additionally, after adjusting for BMI and total energy intake, testosterone levels showed significant negative correlations with PREDIMED score (p < 0.001) and consumption of protein (p = 0.005), complex carbohydrate (p < 0.001), fiber (p < 0.001), MUFA (p < 0.001), n-3 PUFA (p = 0.001), and positive associations with CRP levels, simple carbohydrate, SFA, n-6 PUFA (p < 0.001, respectively), and PUFA (p = 0.002). The cut-off for PREDIMED score ≤ 6 (p < 0.001, area under the curve (AUC) 0.848, standard error 0.036, 95% confidence interval (CI) 0.768 to 0.909) could serve as a threshold for significantly increased risk of high value of testosterone levels. In conclusion, a novel direct association between the adherence to MD and the clinical severity of the disease was reported in women with PCOS. This association could support a therapeutic role of foods and nutrients of the Mediterranean dietary pattern in the PCOS pathogenesis likely involving their inflammatory status, IR, and hyperandrogenemia. In addition, we reported a different body composition that is characterized by lower PhA and fat-free mass than controls. These data suggested a role of PhA as a useful marker of the clinical severity of this syndrome and provided strong evidence regarding the strategic relevance of the nutritional assessment in the management of women with PCOS.

Growing evidence supports the hypothesis that dietary factors may play a role in systemic low-grade chronic inflammation. Summary evidence from randomized controlled trials has shown substantial effects on biomarkers of inflammation following the adoption of plant-based diets (including, but not limited to, the Mediterranean diet), while consistent findings have been reported for higher intakes of whole grains, fruits, and vegetables and positive trends observed for the consumption of legumes, pulses, nuts, and olive oil. Among animal food groups, dairy products have been shown to have the best benefits on biomarkers of inflammation, while red meat and egg have been shown to have neutral effects. The present review provides an overview of the mechanisms underlying the relation between dietary factors and immune system, with a focus on specific macronutrient and non-nutrient phytochemicals (polyphenols) and low-grade inflammation. Substantial differences within each macronutrient group may explain the conflicting results obtained regarding foods high in saturated fats and carbohydrates, underlying the role of specific subtypes of molecules (i.e., short-chain fatty acids or fiber vs. long chain fatty acids or free added sugars) when exploring the relation between diet and inflammation, as well as the importance of the food matrix and the commixture of foods in the context of whole dietary patterns. Dietary polyphenols and oligopeptides have been hypothesized to exert several functions, including the regulation of the inflammatory response and effects on the immune system. Overall, evidence suggests that dietary factors may affect the immune system regardless of obesity-related inflammation.

There is a mechanistic link between the gut-derived metabolite trimethylamine-N-oxide (TMAO) and obesity-related diseases, suggesting that the TMAO pathway may also be linked to the pathogenesis of obesity. The Visceral Adiposity Index (VAI), a gender-specific indicator of adipose dysfunction, and the Fatty Liver Index (FLI), a predictor of non-alcoholic fatty liver disease (NAFLD), are early predictors of metabolic syndrome (MetS). In this cross-sectional observational study, we investigated TMAO levels in adults stratified according to Body Mass Index (BMI) and the association of TMAO with VAI and FLI. One hundred and thirty-seven adult subjects (59 males; 21–56 years) were enrolled. TMAO levels were detected using HPLC/MS analysis. Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), VAI and FLI were included as cardio-metabolic indices. TMAO levels increased along with BMI and were positively associated with VAI and FLI, independently, on common potential covariates. The most sensitive and specific cut-offs for circulating levels of TMAO to predict the presence of NAFLD-FLI and MetS were ≥8.02 µM and ≥8.74 µM, respectively. These findings allow us to hypothesize a role of TMAO as an early biomarker of adipose dysfunction and NAFLD-FLI in all borderline conditions in which overt MetS is not present, and suggest that a specific cut-off of TMAO might help in identifying subjects at high risk of NAFLD.