Natural bioactive constituents from herbs and nutraceuticals promote browning of white adipose tissue.

Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, ß3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.

Chemical Composition and Antibacterial and Antiulcerative Colitis Activities of Essential Oil from Pruni Semen.

This study was sought to investigate the chemical composition and antibacterial and antiulcerative colitis (UC) effects of essential oil from Pruni Semen (PSEO). A GC-MS assay showed that the major compounds in PSEO were products of amygdalin hydrolysis, which possessed great antibacterial and anti-inflammatory potential. In vitro antibacterial experiments demonstrated that PSEO treatment inhibited activity of four kinds of intestinal pathogens probably by disrupting the cell wall. Further in vivo studies showed that PSEO administration significantly improved physiological indexes, attenuated histopathological characteristics, and inhibited proinflammatory cytokine production in dextran sulfate sodium (DSS)-induced UC mice. Network pharmacology and molecular docking results predicted that PSEO might prevent UC via regulating the PI3K/AKT pathway. Western blotting and immunofluorescence assays were further conducted for verification, and the results evidenced that PSEO intervention significantly regulated the PI3K/AKT pathway and the expression of its downstream proteins in DSS-induced mice. PSEO might provide a new dietary strategy for UC treatment.

Flavonoid extracts of Citrus aurantium L. var. amara Engl. Promote browning of white adipose tissue in high-fat diet-induced mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity has become a public burden worldwide due to its booming incidence and various complications, and browning of white adipose tissue (WAT) is recognized as a hopeful strategy to combat it. Blossom of Citrus aurantium L. var. amara Engl. (CAVA) is a popular folk medicine and dietary supplement used for relieving dyspepsia, which is recorded in the Chinese Materia Medica. Our previous study showed that blossom of CAVA had anti-obesity potential, while its role in browning of WAT was still unclear. AIM OF THE STUDY: This study aimed to characterize the constituents in flavonoids from blossom of CAVA (CAVAF) and to clarify the anti-obesity capacities especially the effects on browning of WAT. MATERIALS AND METHODS: Gradient ethanol eluents from blossom of CAVA were obtained by AB-8 macroporous resin. 3T3-L1 cells and pancreatic lipase inhibition assay were employed to investigate the potential anti-obesity effects in vitro. HPLC and UPLC/MS assays were performed to characterize the chemical profiles of different eluents. Network pharmacology and molecular docking assays were used to reveal potential anti-obesity targets. Furthermore, high-fat diet (HFD)-induced mice were constructed to explore the anti-obesity actions and mechanisms in vivo. RESULTS: 30% ethanol eluents with high flavonoid content and great inhibition on proliferation of 3T3-L1 preadipocytes and pancreatic lipase activity were regarded as CAVAF. 19 compounds were identified in CAVAF. Network pharmacology analysis demonstrated that AMPK and PPARα were potential targets for CAVAF in alleviating obesity. Animal studies demonstrated that CAVAF intervention significantly decreased the body weight, WAT weight, serum TG, TC and LDL-C levels in HFD-fed obese mice. HFD-induced insulin resistance and morphological changes in WAT and brown adipose tissue were also markedly attenuated by CAVAF treatment. CAVAF supplementation potently inhibited iWAT inflammation by regulating IL-6, IL-1ß, TNF-α and IL-10 mRNA expression in iWAT of mice. Furthermore, the gene expression levels of thermogenic markers including Cyto C, ATP synthesis, Cidea, Cox8b and especially UCP1 in iWAT of mice were significantly up-regulated by CAVAF administration. CAVAF intervention also markedly increased the expression levels of PRDM16, PGC-1α, SIRT1, AMPK-α1, PPARα and PPARγ mRNA in iWAT of mice. CONCLUSION: CAVAF treatment significantly promoted browning of WAT in HFD-fed mice. These results suggested that flavonoid extracts from blossom of CAVA were probably promising candidates for the treatment of obesity.

p-Synephrine ameliorates alloxan-induced diabetes mellitus through inhibiting oxidative stress and inflammation via suppressing the NF-kappa B and MAPK pathways.

Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.