Lactobacillus reuteri NCIMB 30242 (LRC) Inhibits Cholesterol Synthesis and Stimulates Cholesterol Excretion in Animal and Cell Models.

In this study, we evaluated the effects of Lactobacillus reuteri NCIMB (LRC™) supplementation on hypercholesterolemia by researching its effects on cellular cholesterol metabolism in hypercholesterolemic rats (KHGASP-22-170) and HepG2 cell line. Rats were separated into six groups after adaptation and were then fed a normal control (NC), a high-cholesterol diet (HC), or a HC supplemented with simvastatin 15 mg/kg body weight (positive control [PC]), LRC 1 × 109 colony-forming units (CFU)/rat/day, LRC 4 × 109 CFU/rat/day, or LRC 1 × 1010 CFU/rat/day (1 × 109, 4 × 109, or 1 × 1010). The rats were dissected to study the effects of LRC on cholesterol metabolism and intestinal excretion at the end of experimental period. We discovered that LRC mainly participated in the restraint of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the uptake of low-density lipoprotein (LDL) cholesterol into tissues, partially in the transport of cholesteryl esters into high density lipoprotein for maturation, and intestinal excretion of cholesterol. These results are supported by the expression of transcription factors and enzymes such as HMG-CoA reductase, SREBP2, CYP7A1, CETP, and LCAT in both messenger RNA (mRNA) and protein levels in serum and hepatic tissue. Furthermore, the LRC treatment in HepG2 significantly reduced the mRNA expression of HMG-CoA reductase, SREBP2, and CEPT and significantly increased the mRNA expression of LDL-receptor, LCAT, and CYP7A1 at all doses. Hence, we suggest that LRC supplementation could alleviate the serum cholesterol level by inhibiting the intracellular cholesterol synthesis, and augmenting excretion of intestinal cholesterol.

The Panax ginseng Berry Extract and Soluble Whey Protein Hydrolysate Mixture Ameliorates Sarcopenia-Related Muscular Deterioration in Aged Mice.

Sarcopenia is prevalent as the aging population grows. Therefore, the need for supplements for the elderly is increasing. This study aimed to investigate the efficacy and mechanism of a Panax ginseng berry extract (GBE) and soluble whey protein hydrolysate (WPH) mixture on a sarcopenia-related muscular deterioration in aged mice. Ten-month-old male C57BL/6J mice were administered three different doses of the GBE + WPH mixture for 8 weeks; 700 mg/kg, 900 mg/kg, and 1100 mg/kg. Grip strength, serum inflammatory cytokines level, and mass of muscle tissues were estimated. The deteriorating function of aging muscle was investigated via protein or gene expression. Grip strength and mass of three muscle tissues were increased significantly in a dose-dependent manner, and increased anti-inflammatory cytokine alleviated systemic inflammatory state. The mixture resolved the imbalance of muscle protein turnover through activation of the PI3K/Akt pathway and increased gene expression of the muscle regeneration-related factors, while decreasing myostatin, which interferes with muscle protein synthesis and regeneration. Furthermore, we confirmed that increased mitochondria number in muscle with the improvement of mitochondrial biogenesis. These physiological changes were similar to the effects of exercise.

Codonopsis lanceolata ameliorates sarcopenic obesity via recovering PI3K/Akt pathway and lipid metabolism in skeletal muscle.

BACKGROUND: The incidence of sarcopenic obesity, muscle atrophy induced by obesity, has steadily increased and is emerging as a health problem. Although the anti-obesity effect of Codonopsis lanceolata (CL) is known, its efficacy against sarcopenic obesity has not been studied. PURPOSE: We aimed to investigate the effect of CL on sarcopenic obesity and the changes in the related mechanisms to confirm the potential of CL as an effective natural therapeutic agent for sarcopenic obesity. METHODS: C57BL/6 mice were fed a high-fat diet (HFD) for 9 weeks, and CL was administered for 6 weeks with HFD feeding. Body weight and grip strength were measured twice a week. After sacrifice, muscle fiber histological analysis, blood lipid analysis, muscle triglyceride extraction, western blot, and real-time PCR were performed. High-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS) analysis and in vitro experiments using C2C12 cells were performed to verify the main and active compounds of CL. Confluent C2C12 cells were differentiated for 4 days, and then the main compound of CL was co-treated with palmitic acid for 24 h. RESULTS: CL reduced body weight, mass of three fat tissues (epididymal fat, mesenteric fat, and perirenal fat), adipocyte cross-sectional area (CSA), and improved insulin signaling. Simultaneously, CL improved grip strength, mass of three muscle tissues (quadriceps, gastrocnemius, and soleus), and muscle fiber CSA. These results were due to the recovery of both the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (Akt) signaling pathway and lipid metabolisms in skeletal muscle. Lipids accumulated in skeletal muscle interrupt the PI3K/Akt pathway, but CL reduced intramyocellular triglyceride concentration by restoring gene expression of factors related to triglyceride synthesis and fatty acid oxidation. Therefore, the activated PI3K/Akt pathway enhanced muscle protein synthesis by increasing phosphorylation of ribosomal protein S6 kinase 1 and eIF4E-binding protein 1 and suppressed muscle protein degradation by decreasing expression of muscle ring finger-1 and muscle atrophy F-box protein. In addition, tangshenoside I (TS) was verified as the main compound of CL by HPLC-ESI-MS analysis, and its efficacy of inhibiting myotube atrophy and lipid accumulation in myotubes was confirmed, verifying that TS is an active compound. CONCLUSION: CL is an effective natural material for sarcopenic obesity that suppresses muscle atrophy by inhibiting the accumulation of lipids in skeletal muscle through restoration of impaired PI3K/Akt pathway and lipid metabolism.