Reappraisal of metallothionein: Clinical implications for patients with diabetes mellitus.

Reactive oxygen and nitrogen species (ROS and RNS, respectively) are byproducts of cellular physiological processes of the metabolism of intermediary nutrients. Although physiological defense mechanisms readily convert these species into water or urea, an improper balance between their production and removal leads to oxidative stress (OS), which is harmful to cellular components. This OS may result in uncontrolled growth or, ultimately, cell death. In addition, ROS and RNS are closely related to the development of diabetes and its complications. Therefore, numerous researchers have proposed the development of strategies for the removal of ROS/RNS to prevent or treat diabetes and its complications. Some molecules that are synthesized in the body or obtained from food participate in the removal and neutralization of ROS and RNS. Metallothionein, a cysteine-rich protein, is a metal-binding protein that has a wide range of functions in cellular homeostasis and immunity. Metallothionein can be induced by a variety of conditions, including zinc supplementation, and plays a crucial role in mediating anti-OS, anti-apoptotic, detoxification, and anti-inflammatory effects. Metallothionein can modulate various stress-induced signaling pathways (mitogen-activated protein kinase, Wnt, nuclear factor-κB, phosphatidylinositol 3-kinase, sirtuin 1/AMP-activated protein kinase and fibroblast growth factor 21) to alleviate diabetes and diabetic complications. However, a deeper understanding of the functional, biochemical, and molecular characteristics of metallothionein is needed to bring about new opportunities for OS therapy. This review focuses on newly proposed functions of a metallothionein and their implications relevant to diabetes and its complications.

Antitumor and Immunomodulatory Effect of Gastrodia elata on Colon Cancer In Vitro and In Vivo.

Gastrodia elata Blume (GE) is a well-known kind of herb that has been used in traditional medicine for thousands of years. The extrusion of raw materials from it could improve flavor and enhance bioavailability in food and drug development. The purpose of this study is to investigate antitumor and immune boosting effects of extruded GE in human colon carcinoma cells, splenocytes, and mice-bearing CT26 colon carcinoma cell. Treatment with 100[Formula: see text][Formula: see text]g/mL of extruded GE decreased cell viability and induced the expression of Caspase-3 and Bax in HT29 cells ([Formula: see text]). When we performed DAPI staining, apoptotic bodies with condensed chromatin and fragmented nuclei, known as indicative of apoptotic morphology, increased 24[Formula: see text]h after treatment with 100[Formula: see text][Formula: see text]g/mL of extruded GE. Treatments with extruded GE significantly promoted splenocyte proliferation and IL-2 or IFN-[Formula: see text] secretion, compared with that of control cells ([Formula: see text]). The administration of extruded GE of 200 mg/kg/day decreased tumor growth and Ki-67 or [Formula: see text]-catenin expression in mice ([Formula: see text]). Additionally, we investigated the contents of compounds in extruded GE extracts using ultra performance liquid chromatography. The contents of p-hydroxylbenzyl alcohol and p-hydroxybenzaldehyde in extruded GE were 2.97[Formula: see text]mg/g and 0.04[Formula: see text]mg/g, respectively. It was supposed that antitumor and immunomodulatory effects of extruded GE might exert by the p-hydroxylbenzyl alcohol and p-hydroxybenzaldehyde of many compositions analyzed from extruded GE. These results suggest that extruded GE have the potential to be developed into a natural pharmaceutical and functional food as a cancer chemopreventive agent.

Utilization patterns and cost of complementary and alternative medicine compared to conventional medicine in patients with type 2 diabetes mellitus.

AIMS: We evaluated the use and annual cost of complementary and alternative medicine (CAM) compared to conventional medicine in type 2 diabetes mellitus (DM) in the Korean population. METHODS: We analyzed the database of 2752 DM patients obtained from the Korean National Diabetes Program (KNDP). The cost data of conventional medicine starting 1-year before enrolment of the KNDP were obtained from the hospital electronic database. The cost data of CAM over the same period were obtained from questionnaires. RESULTS: Among the 2752 subjects, 677 patients (24.6%) used CAM, with the most common type being red ginseng and herbal medicine. Patients with a higher income, neuropathy, and self-monitoring of blood glucose (SMBG) were more likely to use CAM. Men, those with a higher education level and income, no cerebrovascular accident (CVA) history, and SMBG showed a relatively higher cost of CAM of total medical cost. The independent predictors for CAM were a higher income, the existence of diabetic neuropathy, no CVA history, and SMBG. CONCLUSIONS: Use and cost of CAM varied depending on income, accompanying complications and SMBG. To evaluate the total medical costs in DM patients, a comprehensive approach considering not only conventional cost but also CAM is required.

Phytoestrogen cimicifugoside-mediated inhibition of catecholamine secretion by blocking nicotinic acetylcholine receptor in bovine adrenal chromaffin cells.

We investigated the effect of the phytoestrogen cimicifugoside, one of the pharmacologically active ingredients of the medicinal plant Cimicifuga racemosa (black cohosh) that has been used to treat many kinds of neuronal and menopausal symptoms, such as arthritis, menopausal depression, and nerve pain. Cimicifugoside inhibited calcium increase induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic acetylcholine receptor (nAChR) agonist in bovine adrenal chromaffin cells with a half-maximal inhibitory concentration (IC(50)) of 18 +/- 2 microM. In contrast, cimicifugoside did not affect the calcium increases evoked by high K(+), veratridine, and bradykinin. The DMPP-induced sodium increase was also inhibited by cimicifugoside with an IC(50) of 2 +/- 0.3 microM, suggesting that the activity of nAChRs is inhibited by cimicifugoside. Cimicifugoside did not affect the KCl-induced secretion but markedly inhibited the DMPP-induced catecholamine secretion that was monitored by carbon-fiber amperometry in real time and high-performance liquid chromatography through electrochemical detection. The results suggest that cimicifugoside selectively inhibits nAChR-mediated response in bovine chromaffin cells.

Inhibition of acetylcholine-mediated effects by borneol.

We previously reported that the aqueous extract from a medicinal plant Dryobalanops aromatica specifically inhibits the nicotinic acetylcholine receptor (nAChR) (Oh et al. Pharmacol Res 2000;42(6):559-64). Here, the effect of borneol, the main constituent of D. aromatica, on nAChR activity was investigated in bovine adrenal chromaffin cells. Borneol inhibited a nAChR agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP)-induced calcium increase with a half maximal inhibitory concentration (IC(50)) of 56+/-9 microM. In contrast, borneol did not affect the calcium increases induced by high K+, veratridine, and bradykinin. The sodium increase induced by DMPP was also inhibited by borneol with similar potency (49+/-12 microM), suggesting that the activity of nAChRs is inhibited by borneol. Borneol inhibited DMPP-induced secretion of [3H]norepinephrine with an IC(50) of 70+/-12 microM. Carbon-fiber amperometry also confirmed the inhibition of DMPP-induced exocytosis by borneol in single chromaffin cells. [3H]nicotine binding, however, was not affected by borneol. The inhibitory effect by borneol is more potent than the effect by lidocaine, a commonly used local anesthetic. The data suggest that borneol specifically inhibits the nAChR-mediated effects in a noncompetitive way.