Jiangtang Sanhao formula ameliorates skeletal muscle insulin resistance via regulating GLUT4 translocation in diabetic mice.

Jiangtang Sanhao formula (JTSHF), one of the prescriptions for treating the patients with diabetes mellitus (DM) in traditional Chinese medicine clinic, has been demonstrated to effectively ameliorate the clinical symptoms of diabetic patients with overweight or hyperlipidemia. The preliminary studies demonstrated that JTSHF may enhance insulin sensitivity and improve glycolipid metabolism in obese mice. However, the action mechanism of JTSHF on skeletal muscles in diabetic mice remains unclear. To this end, high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were subjected to JTSHF intervention. The results revealed that JTSHF granules could reduce food and water intake, decrease body fat mass, and improve glucose tolerance, lipid metabolism, and insulin sensitivity in the skeletal muscles of diabetic mice. These effects may be linked to the stimulation of GLUT4 expression and translocation via regulating AMPKα/SIRT1/PGC-1α signaling pathway. The results may offer a novel explanation of JTSHF to prevent against diabetes and IR-related metabolic diseases.

Lycopene Improves Bone Quality and Regulates AGE/RAGE/NF-кB Signaling Pathway in High-Fat Diet-Induced Obese Mice.

OBJECTIVE: This study was aimed at examining the effects of lycopene on bone metabolism in high-fat diet (HFD)- induced obese mice and to identify the potential underlying mechanisms. METHODS: Mice were fed a HFD for 12 weeks and then continue with or without lycopene intervention (15 mg/kg) for additional 10 weeks. The effects of lycopene on blood glucose and lipid metabolism, as well as serum levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by biochemical assays. Bone histomorphological features and osteoclast activity were assessed by hematoxylin/eosin and tartrate-resistant acid phosphatase staining. Bone microstructure at the proximal tibial metaphysis and diaphysis was determined by microcomputed tomography. Tibial biomechanical strength and material profiles were measured by a three-point bending assay and Fourier transform infrared spectroscopy. Protein expressions involved in the AGE/RAGE/NF-кB signaling pathway were determined by western blot and/or immunohistochemical staining. RESULTS: Lycopene consumption reduced body weight gain and improved blood glucose and lipid metabolism in HFD-induced obese mice. In addition, lycopene treatment preserved bone biomechanical strength, material profiles, and microarchitecture in obese mice. Moreover, these alterations were associated with an increase in serum levels of T-AOC and SOD, and a decline in serum levels of MDA, as well as a reduction of AGEs, RAGE, cathepsin K, and p-NF-кBp65 and NF-кBp65 expressions in the femurs and tibias of obese mice. CONCLUSION: Lycopene may improve bone quality through its antioxidant properties, which may be linked with the regulation of the AGE/RAGE/NF-кB signaling pathway in obese mice. These results suggest that lycopene consumption may be beneficial for the management of obesity-induced osteoporosis.

BaZiBuShen alleviates cognitive deficits and regulates Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways in aging mice.

ETHNOPHARMACOLOGICAL RELEVANCE: BaZiBuShen formula (BZBS) is clinically used to counteract mental fatigue and to retard the aging process. Brain aging echoes in major risks of human sufferings and has become one of the main challenges to our societies and the health-care systems. AIM OF THE STUDY: To investigate the effect and mode of action of BZBS on aging-associated cognitive impairments. MATERIALS AND METHODS: BZBS was orally administered to D-galactose and NaNO2-induced aging mice. Premature senescence was assessed using the Morris water maze, step-down type passive avoidance, and pole-climbing tests. Telomere length was examined by qPCR analysis. Telomerase activity was assessed using PCR ELISA assay. Mitochondrial complex IV activity was examined by biochemical test. The levels of redox and immune status were determined by ELISA or biochemical assay. The expressions of sirtuin 6 (Sirt6), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), P53, telomerase reverse transcriptase (TERT), heme oxygenase-1 (HO-1), phospho(p)-nuclear factor erythroid-2 related factor 2 (NRF2), caspase-3, Bcl-2 associated x (Bax), and B-cell lymphoma-2 (Bcl-2) in the cerebral cortex were examined by Western blot and/or immunohistochemical staining. RESULTS: BZBS intervention ameliorated reduced brain performances in aging mice, including memory, cognitive, and motor functions. In addition, BZBS administration to aging mice preserved redox homeostasis, attenuated immunosenescence, and maintained telomerase activity and telomere length. Moreover, BZBS treatment were associated with a declines in P53, caspase-3, Bax expressions and an increase in Sirt6, p-HO-1, p-NRF2, PGC-1α, and Bcl-2 expressions in the brains of this rapid aging mouse. CONCLUSIONS: BZBS attenuates premature senescence possibly via the preservation of redox homeostasis and telomere integrity, and inhibition of apoptosis in rapid aging mouse. The mechanism governing the alterations may be associated with through the activation of Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways. The results suggest that BZBS may provide a novel strategy for confronting aging and age-associated diseases.

A comprehensive review on the phytochemistry, pharmacokinetics, and antidiabetic effect of Ginseng.

BACKGROUND: Radix Ginseng, one of the well-known medicinal herbs, has been used in the management of diabetes and its complications for more than 1000 years. PURPOSE: The aim of this review is devoted to summarize the phytochemistry and pharmacokinetics of Ginseng, and provide evidence for the antidiabetic effects of Ginseng and its ingredients as well as the underlying mechanisms involved. METHODS: For the purpose of this review, the following databases were consulted: the PubMed Database (https://pubmed.ncbi.nlm.nih.gov), Chinese National Knowledge Infrastructure (http://www.cnki.net), National Science and Technology Library (http://www.nstl.gov.cn/), Wanfang Data (http://www.wanfangdata.com.cn/) and the Web of Science Database (http://apps.webofknowledge.com/). RESULTS: Ginseng exhibits glucose-lowering effects in different diabetic animal models. In addition, Ginseng may prevent the development of diabetic complications, including liver, pancreas, adipose tissue, skeletal muscle, nephropathy, cardiomyopathy, retinopathy, atherosclerosis and others. The main ingredients of Ginseng include ginsenosides and polysaccharides. The underlying mechanisms whereby this herb exerts antidiabetic activities may be attributed to the regulation of multiple signaling pathways, including IRS1/PI3K/AKT, LKB1/AMPK/FoxO1, AGEs/RAGE, MAPK/ERK, NF-κB, PPARδ/STAT3, cAMP/PKA/CERB and HIF-1α/VEGF, etc. The pharmacokinetic profiles of ginsenosides provide valuable information on therapeutic efficacy of Ginseng in diabetes. Although Ginseng is well-tolerated, dietary consumption of this herb should follow the doctors' advice. CONCLUSION: Ginseng may offer an alternative strategy in protection against diabetes and its complications through the regulations of the multi-targets via various signaling pathways. Efforts to understand the underlying mechanisms with strictly-controlled animal models, combined with well-designed clinical trials and pharmacokinetic evaluation, will be important subjects of the further investigations and weigh in translational value of this herb in diabetes management.

Fructus Ligustri Lucidi aqueous extract promotes calcium balance and short-chain fatty acids production in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL) is an edible herb with anti-osteoporotic activity, yet whether and how the aqueous extract of this herb affect calcium metabolism in preservation of bone quality remain unclear. AIM OF THE STUDY: To investigate the effects of FLL aqueous extract on calcium balance and short-chain fatty acids (SCFAs) production in ovariectomized (OVX) rats. MATERIALS AND METHODS: OVX rats were daily and orally administrated with FLL aqueous extract (3.5 g/kg) for 14 weeks. The levels of N-terminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTx-I) in rat serum were evaluated by ELISA assays. The concentration of calcium in serum, urine, and feces were determined by biochemical assays. Bone quality was determined by Micro-CT, a three-point bending assay, and Fourier Transform Infrared (FTIR) Spectrometry. The expressions of Calbindin D28K and Calcium-sensing receptor (CaSR) in kidney as well as the Vitamin D receptor (VDR), the transient receptor potential vanilloid receptor 6 (TRPV6), Calbindin D9k in the duodenum were measured by immunohistochemistry, western blotting, or real-time PCR. The short-chain fatty acids (SCFAs) levels in the feces of the cecum were tested by gas chromatograghy. RESULTS: The administration of FLL to OVX rats resulted in a significant improvement in bone mineral density and biomechanical strength as well as in maintaining bone microstructures and material quality. Meanwhile, the decreased levels of PINP and increased levels of CTx-I in OVX rats were restored by FLL treatment. Additionally, FLL treatment increased calcium absorption, upregulated VDR, TRPV6, Calbindin D9k expressions in the duodenum, Calbindin D28K in kidney, and down-regulated CaSR expression in the kidney, as well as enhanced SCFAs levels in the feces of OVX rats. CONCLUSIONS: FLL aqueous extract may preserve bone quality through regulation of the calcium balance and intestinal SCFAs production in OVX rats. This offers translational value of FLL into osteoporosis clinical trial.