caryophyllene and Diabetes-Mellitus--Type-2

Beta-caryophyllene (BCP) is a flavoring agent, whereas l-arginine (LA) is used as a food supplement. They possess insulinotropic and β cell regeneration activities, respectively. We assessed the antidiabetic potential of BCP, LA, and its combination in RIN-5F cell lines and diabetic rats. Ex vivo studies were carried out for glucose uptake and absorption of the combination of BCP with LA. The results indicated that the combination of BCP with LA showed a significant decrease in glucose absorption and an increase in its uptake in tissues and also an increase in insulin secretion in RIN-5F cells. The combination treatment of BCP with LA showed a significant reduction in glucose, lipid levels, and oxidative stress in pancreatic tissue when compared with the diabetic group. Furthermore, the combination of BCP with LA normalized glucose tolerance and pancreatic cell damage in diabetic rats. In conclusion, the combinational treatment showed significant potentials in the treatment of type 2 diabetes mellitus. PRACTICAL APPLICATIONS: Type 2 diabetes mellitus is the most prevalent chronic metabolic disorder affecting a large population. Beta-caryophyllene is a CB

Topics: Animals; Arginine; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Polycyclic Sesquiterpenes; Rats

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of the development of colorectal cancer (CRC). A previous study revealed that the levels of arginine-specific mono-ADP-ribosyltransferase 1 (ART1) in CRC tissues from patients with T2DM were higher than in non-diabetic patients. Hyperglycemia, which is a risk factor of cancer, is a common feature of T2DM; however, the effects of ART1 on glycolysis and energy metabolism in CRC cells under high-glucose conditions remains to be elucidated. β-caryophyllene (BCP) has been reported to exert anticancer and hypoglycemic effects. In the present study, CT26 cells were cultured under a high-glucose conditions and the expression levels of relevant factors were detected by western blotting. Cell Counting Kit-8 assay, flow cytometry, Hoechst 33258 staining, ATP assay and lactic acid assay were used to detect the proliferation, apoptosis and energy metabolism of CT26 cells. To observe the effects of ART1 and BCP on tumor growth in vivo, CT26 cell tumors were successfully transplanted into BALB/c mice with T2DM. The results demonstrated that overexpression of ART1 may increase glycolysis and energy metabolism in CT26 CRC cells under high glucose conditions by regulating the protein kinase B/mammalian target of rapamycin/c‑Myc signaling pathway and the expression of glycolytic enzymes. BCP inhibited the effects induced by ART1, which may be due to a BCP-induced reduction in the expression levels of ART1 via nuclear factor-κB. Therefore, ART1 may be considered a therapeutic target for the treatment of diabetic patients with CRC.

Topics: ADP Ribose Transferases; Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Energy Metabolism; Glucose; Glycolysis; GPI-Linked Proteins; Humans; Male; Mice; Mice, Inbred BALB C; Polycyclic Sesquiterpenes; RNA, Small Interfering; Sesquiterpenes; Signal Transduction; Streptozocin; Xenograft Model Antitumor Assays

Painful distal symmetric polyneuropathy (pDSPN) is one of the most common and invalidating complications of diabetes mellitus, both of type 1 and type 2. Mechanisms responsible for the occurrence of the pDSPN are multifactorial and involve metabolic pathways regulating inflammation, microvessel circulation, axonal degeneration and so on. Several therapeutic approaches have been proposed to treat pain and each of them showed positive effects associated to drug-related side effects.. Twenty-five consecutive patients with diagnosis of diabetes mellitus and pDSPN and tried to manage pain with a dietary supplement composed of a mixture of natural extracts (β-caryophyllene, myrrh, carnosic acid) and PEA. This is a nutraceutical with potential multiple effects on metabolic, pain and vascular compartments, a profile considered useful in pDSPN. Patients were enrolled and polyneuropathy evaluated by means of nerve conduction study. Pain was assessed using VAS score scale and MNSI. Each patient was evaluated at T0 (time of enrollment) and at T1 (after 16 weeks of treatment).. Supplement administration was well tolerated and induced unexpectedly significant amelioration of polyneuropathy with increase amplitude and reduction of pain. No side effects were reported.. This fixed combination could well be considered as a potential nutraceutical option to manage pDSPN in diabetic patients.

Topics: Abietanes; Adult; Amides; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dietary Supplements; Ethanolamines; Female; Humans; Male; Pain Measurement; Palmitic Acids; Polycyclic Sesquiterpenes; Sesquiterpenes; Severity of Illness Index; Sural Nerve; Terpenes; Treatment Outcome; Young Adult

Glucose-stimulated insulin secretion (GSIS) is essential for the control of metabolic fuel homeostasis and its impairment is a key element in the failure of β-cells in type 2 diabetes. Trans-caryophyllene (TC), an important constituent of the essential oil of several species of plants, has been reported to activate the type 2 cannabinoid receptor (CB2R). The effects of TC on GSIS are still unknown. Our results demonstrate that administration of TC in MIN6 cells promotes GSIS in a dose dependent manner. However, inhibition of CB2R by a specific inhibitor or specific RNA interference abolished the effects of TC on GSIS, which suggests that the effects of TC on GSIS are dependent on activation of CB2R. Further study demonstrated that treatment with TC leads to the activation of small G protein Arf6 as well as Rac1 and Cdc42. Importantly, Arf6 silencing abolished the effects of TC on GSIS, which suggests that Arf6 participates in mediating the effects of TC on GSIS. We conclude from these data that TC has a novel role in regulating GSIS in pancreatic β-cells.

Topics: ADP-Ribosylation Factor 6; ADP-Ribosylation Factors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Diabetes Mellitus, Type 2; Glucose; Insulin; Insulin-Secreting Cells; Mice; Polycyclic Sesquiterpenes; Receptor, Cannabinoid, CB2; Sesquiterpenes