Dysfunction of glucose metabolism is associated with the occurrence of metabolic syndromes, including type 2 diabetes mellitus (T2DM). In this study, we investigated the anti-diabetic effects of yam extract and allantoin in high-fat-diet (HFD) and streptozotocin (STZ)-induced diabetic mice and the mechanism of action on the dysfunction of the liver, pancreas, and skeletal muscle. Male C57BL/6 mice were induced into a diabetic condition by HFD for 16 weeks and a single injection of STZ (120 mg/kg) and then orally administered yam extract (500 and 1000 mg/kg) or allantoin (20 and 50 mg/kg) once daily for 4 weeks. The changes in physiological parameters, serological parameters, and morphology of tissues were investigated. The expression levels of antioxidant enzymes, biogenetic proteins, and myogenetic proteins were determined in the liver, pancreas and skeletal muscle tissues of mice. The administration of yam extract and allantoin at high doses in HFD-/STZ-induced diabetic mice compared with the control group significantly decreased the increase in body weight, caloric intake, and water intake. Yam extract and allantoin significantly decreased high glucose and leptin, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, aspartate transaminase, alanine aminotransferase levels and increased insulin and albumin levels in the plasma of mice. Yam extract and allantoin inhibited the structural damage of the liver with regard to fat accumulation, the pancreas with regard to hyperplasia of Langerhans' islets, and skeletal muscle with regard to atrophy and significantly increased the expression of antioxidant enzymes and mitochondria-mediated biogenetic factors in the liver, pancreas, and muscle tissues. In addition, yam extract and allantoin significantly increased the expression of myogenetic proteins in skeletal muscle tissues. Our results indicated that yam extract and allantoin improve diabetic symptoms through the regulation of oxidation and glucose imbalance in liver, pancreas, and skeletal muscle tissues in mice. These findings suggest that yam extract and allantoin can be used as antidiabetic factors in supplementary foods and medications for T2DM patients.

Daphnes Cortex (Daphne Giraldii Nitsche, DGN) is a popular traditional Chinese herbal medicine for traumatic injuries and rheumatoid arthritis (RA) in the Shaanxi and Gansu provinces of China. Due to skin irritation caused by raw DGN (RDGN), licorice-processed DGN products are usually used in clinical practice. However, the efficacy and mechanisms of action between DGN and its licorice-processed DGN products in treating RA have not been compared. This study compared the efficacy and elucidated the mechanisms in vitro and in vivo between RDGN and its licorice-processed DGN products in treating RA. A collagen-induced RA rat model was established, and treated with different doses of RDGN and its licorice-processed DGN products for 4 weeks to explore the therapeutic effects. The anti-inflammatory effects were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). Analyses of the differential quality markers (DQMs) between DGN and its licorice-processed DGN products using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and non-targeted metabolomics analyses of rat synovial tissues were used to systematically explore correlations between DGN processing and its efficacy. Licorice-processed DGN products significantly ameliorated RA symptoms in CIA rats. Licorice-processed DGN products also regulated inflammatory cytokines, matrix metalloproteinases, and vascular endothelial growth factor in the serum and cell supernatants. Licorice-processed DGN products significantly inhibited Toll-like receptor 4/nuclear factor kappa B/NOD-like receptor family, pyrin domain containing 3 (TLR4/NF-κB/NLRP3) signaling in CIA rats and LPS-induced RAW264.7 cells. The DQMs between RDGN and its licorice-processed DGN products were identified, most of which were amino acids or energy-related metabolites present in licorice-processed DGN products. Correlations between DQMs with differential metabolites and differential metabolic pathways were established. Licorice-processed DGN products displayed better anti-inflammatory effects via the TLR4/NF-κB/NLRP3 signaling pathway on CIA rats and LPS-induced RAW264.7 cells, and regulation of the metabolic profile in treating RA.

With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (Sirt-1), nuclear respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total ATP contents were measured by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased glucose uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated myoblast differentiation into myotubes and increased energy production through the upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent skeletal muscle dysfunction through the stimulation of the energy metabolism.

Our study was conducted to investigate the effects of the fruits of Lycium chinense Mill. (Lycii Fructus, LF) and its bioactive compound, betaine, on muscle differentiation and mitochondrial biogenesis in C2C12 cells. LF extract and betaine was analyzed by high-performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and peroxisome proliferator-activated receptor gamma coactivator1-alpha (PGC-1α), sirtuin-1(Sirt-1), nuclear respiratory factor-1 (NRF-1), transcription factor A, mitochondrial (TFAM) and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), were determined in cellular or mitochondrial levels by quantitative polymerase chain reaction (qPCR) or Western blot, respectively. The glucose levels and total ATP contents were measured by the glucose consumption in a culture medium, cellular glucose uptake and ATP assays. LF extract at 4 mg/ml and betaine at 2 and 5 mM significantly increased the expression of MyHC in C2C12 myotubes, compared with non-treated cells. LF extract and betaine significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM mRNA and protein in the myotubes, as well as phosphorylation of AMPK and ACC. Furthermore, LF extract and betaine significantly increased the mitochondrial protein contents, as the TFAM and NRF-1 expressions were increased. LF extract and betaine also significantly increased the glucose uptake and ATP contents in the myotubes. The LF extract contained 3.18% betaine was quantitated by HPLC. LF extract and betaine enhanced muscle differentiation and energy metabolism through the up-regulation of mitochondrial biogenesis-regulating factors, suggesting that LF extract and betaine can help to prevent the dysfunction of skeletal muscle.

Carbonization of Radix Rehmanniae Preparata (Shu Dihuangtan) via stir-frying could increase its homeostasis maintaining and antidiarrheal effects. To ensure these pharmacological functions, the quality of the raw material (processed Rehmanniae Radix) must be well controlled. Therefore, we analyzed the effects of different degrees of processing and adjuvants on processed Rehmanniae Radix (Shu Dihuang) by High Performance Liquid Chromatography (HPLC) chromatographic fingerprints, thermal gravimetric analysis and Fourier transform infrared spectroscopy (FTIR). Based on the results from HPLC fingerprints combined with similarity analysis (SA) and hierarchical cluster analysis (HCA) the optimum processing method for Shu Dihuang was five cycles of steaming and polishing, which follows the ancient processing theory. The intensity of thermal weight loss rate peaked near 210.33 ± 4.32 °C or 211.33 ± 2.62 °C, which was an important indicator for the degree of processing of Shu Dihuang. A temperature near 290.89 ± 2.51 °C was the upper limit for carbonizing Shu Dihuangtan. FTIR spectroscopy analysis showed that the overall chemical composition of Shu Dihuangtan was affected by both the degree of processing and adjuvant, which are very important for its quality.

Bombyx batryticatus (BB) is one of the most commonly used Traditional Chinese Medicines (TCMs) in the treatment of convulsions and epilepsy. The antiepileptic effects of total proteins from BB (BBPs) have been proven in our previous research. In this study, BBPs were further purified, the neuroprotective effects were evaluated in Glu-stimulated PC12 cells, and the structure was identified by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Six subfractions (PF-1 to PF-6) were obtained by DEAE-52 Sepharose FF ion-exchange chromatography. It was found that PF-1, PF-2, and PF-3, with similar protein compositions, possessed neuroprotective effects in Glu-stimulated PC12 cells by significantly increasing the GABA level, and decreasing the levels of IL-1β and TNF-α. The most active fraction (PF-2) was further separated by Sephadex G-75 gel filtration chromatography, and an effective protein component named PF-2-2 was obtained. Fluorescein isothiocyanate-labeled PF-2-2 (FITC-PF-2-2) was prepared, and the binding of FITC-F-2-2 to the PC12 cells was directly observed with a confocal microscope. PF-2-2 was found to first bind to the surface of PC12 cells and then internalize into the cells. The main band of PF-2-2 was then analyzed by MALDI-TOF/TOF-MS and searched in the MASCOT database; finally a protein named Low molecular mass 30 kDa lipoprotein 21G1 was identified. In conclusion, PF-2-2 and purified proteins isolated from BBPs have potential application prospects in the treatment of epilepsy.