Elevated levels of plasma free fatty acid (FFA) and disturbed mitochondrial dynamics play crucial roles in the pathogenesis of diabetic kidney disease (DKD). However, the mechanisms by which FFA leads to mitochondrial damage in glomerular podocytes of DKD and the effects of Berberine (BBR) on podocytes are not fully understood.

Background and Purpose: Disordered lipid metabolism and disturbed mitochondrial bioenergetics play pivotal roles in the initiation and development of diabetic kidney disease (DKD). Berberine is a plant alkaloid, used in Chinese herbal medicine. It has multiple therapeutic actions on diabetes mellitus and its complications, including regulation of glucose and lipid metabolism, improvement of insulin sensitivity, and alleviation of oxidative damage. Here, we investigated the reno‐protective effects of berberine.Experimental Approach: We used samples from DKD patients and experiments with models of DKD (db/db mice) and cultured podocytes, to characterize energy metabolism profiles using metabolomics. Molecular targets and mechanisms involved in the regulation of mitochondrial function and bioenergetics by berberine were investigated, along with its effects on metabolic alterations in DKD mice.Key Results: Metabolomic analysis suggested altered mitochondrial fuel usage and generalized mitochondrial dysfunction in patients with DKD. In db/db mice, berberine treatment reversed the disordered metabolism, podocyte damage and glomerulosclerosis. Lipid accumulation, excessive generation of mitochondrial ROS, mitochondrial dysfunction, and deficient fatty acid oxidation in DKD mouse models and in cultured podocytes were suppressed by berberine. These protective effects of berberine were accompanied by activation of the peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) signalling pathway, which promoted mitochondrial energy homeostasis and fatty acid oxidation in podocytes.Conclusion and Implications: PGC‐1α‐mediated mitochondrial bioenergetics could play a key role in lipid disorder‐induced podocyte damage and development of DKD in mice. Restoration of PGC‐1α activity and the energy homeostasis by berberine might be a potential therapeutic strategy against DKD.

Objectives.To assess the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus (T2DM).Methods.Randomized trials of berberine compared with lifestyle modification, placebo, and/or oral hypoglycaemics intervention on treating T2DM were included. Study population characteristics and outcome results were extracted independently by two reviewers. Meta-analyses were performed for data available.Results.Fourteen randomized trials, involving 1068 participants, were included in this study. Methodological quality was generally low. Compared with lifestyle modification with or without placebo, the cointervention of berberine and lifestyle modification showed significantly hypoglycaemic and antidyslipidemic response. Compared with oral hypoglycaemics including metformin, glipizide, or rosiglitazone, berberine did not demonstrate a significantly better glycaemic control but showed a mild antidyslipidemic effect. Compared with oral hypoglycaemic drugs, cointerventions with berberine and the same oral hypoglycaemics showed a better glycaemic control. No serious adverse effects from berberine were reported.Conclusions.Berberine appeared to be efficacious for treating hyperglycaemia and dyslipidemia in T2DM. However, the evidence of berberine for treating T2DM should be carefully interpreted due to the low methodological quality, small sample size, limited number of trials, and unidentified risks of bias.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is characterized by excessive hepatic lipid accumulation. Many studies have suggested that lipid overload is the key initial factor that contributes to hepatic steatosis. Our previous study indicated that diosgenin (DSG) has a beneficial effect on energy metabolism, but the underlying mechanism remains unclear. Methods: Human normal hepatocytes (LO2 cells) were incubated with palmitic acid to establish the cell model of nonalcoholic fatty liver. The effects of DSG on lipid metabolism, glucose uptake and mitochondrial function were evaluated. Furthermore, the mechanism of DSG on oxidative stress, lipid consumption and lipid synthesis in LO2 cells was investigated. Results: The results indicated that palmitic acid induced obvious lipid accumulation in LO2 cells and that DSG treatment significantly reduced the intracellular lipid content. DSG treatment upregulated expression of lipolysis proteins, including phospho-AMP activated protein kinase (p-AMPK), phospho-acetyl-coA carboxylase (p-ACC) and carnitine acyl transferase 1A (CPT-1A), and inhibited expression of lipid synthesis-related proteins, including sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS). Additionally, DSG-treated cells displayed a marked improvement in mitochondrial function, with less production of reactive oxygen species and a higher mitochondrial membrane potential compared with the model group. Conclusion: This study suggests that DSG can reduce intracellular lipid accumulation in LO2 cells and that the underlying mechanism may be related to the improving oxidative stress, increasing fatty acid β-oxidation and decreasing lipid synthesis. The above changes might be mediated by the activation of the AMPK/ACC/CPT-1A pathway and inhibition of the SREBP-1c/FAS pathway.

Clinical trials have reported lipid-lowering effects of berberine intake, but the findings have been inconsistent. The aim of this meta-analysis was to assess the safety of berberine and its effects on blood lipid profiles. A systemic review was designed, undertaken and reported in accordance with the PRISMA statement. Randomized controlled trials of the effects of berberine on blood lipids in adults were included. Study population characteristics and the main results, including changes in the levels of total cholesterol, triglycerides, low-density and high-density lipoprotein cholesterol, were extracted. Weighted mean differences were calculated for net changes in blood lipid concentrations using fixed-effect or random-effects models. After filtering, eleven randomized controlled trials (including a total of 874 participants) were included in this study. The methodological quality of these studies was generally low. The final analysis showed that administration of berberine produced a significant reduction in total cholesterol (mean difference − 0.61 mmol/L; 95 % confidence interval − 0.83 to − 0.39), triglycerides (mean difference − 0.50 mmol/L; 95 % confidence interval − 0.69 to − 0.31), and low-density lipoprotein cholesterol (mean difference − 0.65 mmol/L; 95 % confidence interval − 0.76 to − 0.54) levels, with a remarkable increase in high-density lipoprotein (mean difference 0.05 mmol/L; 95 % confidence interval 0.02 to 0.09). No serious adverse effects of berberine have been reported. In conclusion, berberine may have beneficial effects in the control of blood lipid levels. However, the efficacy of berberine in treating hyperlipidemia should be further evaluated by more randomized controlled trials in a larger population of patients. ^* Equal contribution.

Aim: The new coronavirus (COVID-19) pneumonia outbreaking at the end of 2019 is highly contagious. Crude mortality rate reached 49% in critical patients. Inflammation matters on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. Methods: In this cross-sectional study, 100 patients were included and divided to mild, severe or critical groups. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. Results: Significantly, disease severity was associated with age (R=-0.564, P<0.001), interleukin-2 receptor (IL2R) (R=-0.534, P<0.001), interleukin-6 (IL-6) (R=-0.535, P<0.001), interleukin-8 (IL-8) (R=-0.308, P<0.001), interleukin-10 (IL-10) (R=-0.422, P<0.001), tumor necrosis factor α (TNFα) (R=-0.322, P<0.001), C-reactive protein (CRP) (R=-0.604, P<0.001), ferroprotein (R=-0.508, P<0.001), procalcitonin (R=-0.650, P<0.001), white cell counts (WBC) (R=-0.54, P<0.001), lymphocyte counts (LC) (R=0.56, P<0.001), neutrophil count (NC) (R=-0.585, P67.5 years, IL2R >793.5U/mL, CRP >30.7ng/mL, ferroprotein >2252μg/L, WBC>9.5*10^9/L or NC >7.305*10^9/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Inflammation is closely related to severity of COVID-19, and IL-6, TNFα and IL-8 might be promising therapeutic targets.