The phenolic profiles, hypoglycemic activity, and molecular mechanism of the effect on type 2 diabetes mellitus (T2DM) of four highland barley varieties were investigated in the present study. The fundamental phenolics in highland barley were ferulic acid, naringin, and catechin, which mainly existed in bound form. These varieties showed favorable hypoglycemic activity via inhibition of α-glucosidase and α-amylase activities, enhancement of glucose consumption, glycogen accumulation and glycogen synthase 2 (GYS2) activity, and down-regulation of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities. Specifically, ZQ320 variety exhibited the strongest hypoglycemic activity compared to the other varieties. Highland barley phenolics could inhibit gluconeogenesis and motivate glycogen synthesis via down-regulating the gene expression of G6Pase, PEPCK, and glycogen synthase kinase 3β (GSK3β), while activating the expression of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3 kinase (PI3K), serine/threonine kinase (Akt), GYS2, and glucose transporter type 4 (GLUT4). Therefore, phenolics from highland barley could be served as suitable candidates for therapeutic agent in T2DM to improve human health.

The effects of Rhodiola extract (RE) on longevity and stress resistance in Caenorhabditis elegans (C. elegans), and the underlying molecular mechanisms were explored in the present study. Results showed that the lifespan of C. elegans was remarkably prolonged by 37.1% after treated with high-dose RE (480 μg mL⁻¹). Intervention with RE alleviated aging-related declines in the C. elegans model, and enhanced the stress resistance against heat shock, ultraviolet radiation and paraquat. Moreover, RE reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and catalase (CAT). RE also upregulated the gene expression of sod-3, gst-4, daf-16, skn-1 in C. elegans, downregulated the gene expression of daf-2 and age-1, and accelerated the translocation of DAF-16 and SKN-1 into the nucleus. Furthermore, the daf-16(mu86) and skn-1(zu169) mutants reversed the extension of lifespan triggered by RE, indicating that these genes were involved in RE-regulated longevity. These results demonstrated that RE could enhance lifespan extension, healthspan and stress resistance of C. elegans via insulin/IGF signaling and SKN-1 pathways. Therefore, the present findings suggested Rhodiola as a potential candidate to ameliorate the symptoms of aging.

Orange, with various bioactive phytochemicals, exerts various beneficial health effects, including anti-cancer, antioxidant, and anti-inflammatory properties. However, its anti-aging effects remain unclear. In this study, the Caenorhabditis elegans (C. elegans) model was used to evaluate the effects of orange extracts on lifespan and stress resistance. The results indicated that orange extracts dose-dependently increased the mean lifespan of C. elegans by 10.5%, 18.0%, and 26.2% at the concentrations of 100, 200, and 400 mg/mL, respectively. Meanwhile, orange extracts promoted the healthspan by improving motility, and decreasing the accumulation of age pigment and intracellular reactive oxygen species (ROS) levels without damaging fertility. The survival rates of orange extract-fed worms were obviously higher than those of untreated worms against thermal and ultraviolet-B (UV-B) stress. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly enhanced while malondialdehyde (MDA) contents were diminished. Further investigation revealed that worms supplemented with orange extracts resulted in upregulated levels of genes, including daf-16, sod-3, gst-4, sek-1, and skn-1, and the downregulation of age-1 expression. These findings revealed that orange extracts have potential anti-aging effects through extending the lifespan, enhancing stress resistance, and promoting the healthspan.

The effects of whole grain highland barley (WGH) with rich phenolics on glucose metabolism, the insulin pathway, and microRNA (miRNA) expression in db/db mice were explored in the present study. Supplementation with WGH decreased the levels of blood glucose, glycosylated serum protein (GSP), insulin, and inflammatory cytokines in db/db mice. Furthermore, WGH administration triggered a remarkable amelioration of glucose intolerance and insulin resistance. The hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK) activities and the G6PC, PEPCK, and forkhead transcription factor 1 (FOXO1) mRNA levels in the WGH-treated group were also reduced. Moreover, WGH promoted the glycogen storage in the liver via up-regulating the activities of hexokinase (HK) and glycogen synthase (GS) and the phosphorylation of glycogen synthase kinase 3β (GSK3β) protein, while down-regulating the GSK3β mRNA level. The protein expression of phosphatidylinositol 3-kinase (PI3K), the phosphorylation of protein kinase B (Akt), and the mRNA levels of insulin receptor substrate-1 (IRS-1), PI3K and Akt were also up-regulated by WGH treatment. Moreover, WGH significantly augmented the expression of miRNA-26a and miRNA-451, but reduced those of miRNA-126a and miRNA-29a. These results demonstrated that WGH exhibits a hypoglycemic effect through regulating the IRS-1/PI3K/Akt pathway and related miRNAs, further modulating the expression of G6PC, PEPCK, and FOXO1 mRNAs and p-GSK3β protein, thus inhibiting hepatic gluconeogenesis, improving glycogen synthesis and alleviating insulin resistance. Therefore, this study suggested WGH as an effective candidate to ameliorate the hyperglycemia of type 2 diabetes mellitus.

Present study further unravels the underlying mechanism of Goji berry on the lifespan of C. elegans : IIS, HSF, and SIR-2.1 pathways.