Metformin is the most widely used drug to treat type 2 diabetes, and is one of only two oral antidiabetic drugs on the World Health Organization (WHO) list of essential medicines. Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. However, we still do not completely understand its mechanisms of action. The main effect of this drug from the biguanide family is to acutely decrease hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory chain complex I. In addition, the resulting decrease in hepatic energy status activates AMPK (AMP-activated protein kinase), a cellular metabolic sensor, providing a generally accepted mechanism for the action of metformin on hepatic gluconeogenesis. The use of metformin, the most commonly prescribed drug for type 2 diabetes, was repeatedly associated with the decreased risk of the occurrence of various types of cancers, especially of pancreas and colon and hepatocellular carcinoma.

8-chloroadenosine (8-Cl-Ado) is a ribonucleoside analog. The mechanism of its action remains poorly understood, however, it is known that the drug inhibits RNA synthesis. It has significant cytotoxic activity against lymphoid and myeloid malignant cells. The nucleoside analog 8-Cl-Ado is phosphorylated into its cytotoxic triphosphate 8-Cl-ATP. The accumulation of the cytotoxic metabolite results in a parallel decrease of the ATP cellular pools. 8-Cl-Ado gets incorporated into RNA during transcription, hindering this process. In addition, this triphosphate inhibits ATP-dependent poly(A) tail synthesis, and, as a consequence, mRNA processing is inhibited, resulting in vitro cytotoxicity in several solid and hematological malignancies. This agent is currently in clinical trials for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia.

A-769662 stimulates partially purified rat liver AMPK with EC50 with 0.8 uM. A-769662 activates AMPK purified from multiple tissues and species in a dose-responsive manner with modest variations in observed EC50s. EC50s determined for A-769662 using partially purified AMPK extracts from rat heart, rat muscle, or human embryonic kidney cells (HEKs) are 2.2 uM, 1.9 uM, or 1.1 uM, respectively. A 4 hours treatment of primary rat hepatocytes with A-769662 dose-dependently increases ACC phosphorylation, which correlated inhibition of fatty acid synthesis with IC50 of 3.2 uM. A-769662 also inhibits fatty acid sythesis in mouse hepatocytes with IC50 with 3.6 uM. A-769662 activates AMPK both allosterically and by inhibiting dephosphorylation of AMPK on Thr-172, similar to the effects of AMP. A-769662 inhibits proteasomal function by an AMPK-independent mechanism. A-769662 affects the in vitro activity of purified 26S proteasomes but not the in vitro activity of purified 20S proteasomes. A-769662 has toxic effects on MEF cells. A recent research shows A-769662 inhibited cell proliferation and DNA synthesis.

Phillyrin, an active ingredient found in many medicinal plants and certain functional foods, elicits anti-obesity and anti-inflammatory properties in vivo. Phillyrin is one of the main chemical constituents of Forsythia suspensa (Thunb.), which has shown to be an important traditional Chinese medicine. Phillyrin, has being shown to possess various bioactivities, including anti-inflammatory, anti-oxidant, and antiviral activities. It has being reported that Phillyrin attenuates high glucose-induced lipid accumulation in human HepG2 hepatocytes through the activation of LKB1/AMP-activated protein kinase-dependent signalling.

Phenformin is a biguanide hypoglycemic agent with actions and uses similar to those of metformin. It activates AMP-activated protein kinase (AMPK) and inhibits mTORC1 signaling. Phenformin used for the treatment of diabetes. Phenformin was removed from the U.S. market 20 years ago because of a high incidence of lactic acidosis. Risk factors for the development of lactic acidosis include renal deficiency, hepatic disease, cardiac disease, and drug interaction such as cimetidine. Phenformin exerts potential anti-neoplastic action.

Danthron, a natural product, was originally extracted from the roots and rhizome of Polygonaceae plant. Danthron is an anthraquinone. Danthron has been widely administrated as a laxative since the 1900s. In the United States, danthron has been forbidden to continual use as laxative because it is considered to be a carcinogen. In the UK, it is not marketed alone but in combination with poloxamer 188 as co-danthramer and with docusate as co-danthrusate; in the UK, its use is strictly restricted to the elderly and to the terminally ill of all ages because of concerns about carcinogenicity and hepatotoxicity. It has only a limited role in the treatment of constipation.

2-deoxyglucose is predominantly used as a diagnostic agent in its radiolabelled form (fluorine-18 is used as the radiolabel). Therapeutically, 2-deoxyglucose is an investigational drug that is being studied as an anticancer and antiviral agent. The exact mechanisms of action of 2-deoxyglucose is still being investigated, but it is known that in hypoxic cancer cells, 2-deoxyglucose is a glycolysis inhibitor that prevents ATP production and, ultimately, cell survival. With respect to antiviral therapy, 2-deoxyglucose was shown to be effective against herpes simplex virus by affecting the virus' ability to penetrate cells. As an experimental drug, 2-deoxyglucose was demonstrated to work as an anticonvulsant in temporal lobe epilepsy. In this condition, 2-deoxyglucose represses the expression of certain proteins that are at high levels after a seizure. Although there are several possible therapeutic indications for 2-deoxyglucose, presently there is no approved indication for 2-deoxyglucose as a therapeutic agent.

Ginsenoside C is a triterpene saponin originally found in species of Panax (ginseng) that exhibits anti-osteoporotic, antioxidative, antiviral, anti-hyperlipidemic, anti-metastatic, anti-angiogenic, and anticancer chemotherapeutic activities. In vivo, ginsenoside C decreases levels of malondialdehyde and increases levels of glutathione, improving bone microarchitecture and bone mineral density. In other animal models, this compound decreases virus titers and protects against infection of hemagglutinating virus of Japan. In adipocytes, ginsenoside C decreases levels of cholesterol and triglycerides and increases expression of SREBP. In uterine endometrial cancer cells, ginsenoside C decrease expression of matrix metalloproteinase 2 (MMP2), suppressive cellular invasion; this compound also inhibits neovascularization and tumor growth in animal models of melanoma. Ginsenoside C is a component of Korean Red Ginseng, marketed in Korea. Korean ginseng (Panax ginseng Meyer, Araliaceae) is traditionally used as an important herbal medicine in Far East Asia. Korean Red Ginseng is possibly effective for: • Alzheimer's disease. Evidence shows that taking Panax ginseng root daily for 12 weeks can improve mental performance in people with Alzheimer's disease. • Lung disease called chronic obstructive pulmonary disease (COPD). Taking Panax ginseng by mouth seems to improve lung function and some symptoms of COPD. • Mental function. Taking Panax ginseng by mouth might improve abstract thinking, mental arithmetic skills, and reaction times in healthy, middle-aged people but not in young adults. Panax ginseng alone does not seem to improve memory. But there is some evidence that a combination of Panax ginseng and ginkgo leaf extract can improve memory in otherwise healthy people between the ages of 38 and 66. • Erectile dysfunction (ED). Taking Panax ginseng by mouth seems to improve sexual function in men with erectile dysfunction. • Flu. Taking a specific Panax ginseng by mouth appears to reduce the risk of getting a cold or the flu. But, taking Panax ginseng does not seem to reduce flu symptoms or the length of the illness. • Multiple sclerosis-related fatigue. Taking Panax ginseng daily for 3 months reduces feelings of tiredness and improves quality of life in females with MS. • Premature ejaculation. Applying a cream containing Panax ginseng, angelica root, Cistanches deserticola, Zanthoxyl species, torlidis seed, clover flower, asiasari root, cinnamon bark, and toad venom (SS Cream) to the penis one hour before intercourse and washing off immediately before intercourse seems to help prevent premature ejaculation.

Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. It works by enhancing mucosal defense, scavenging free radicals, and temporarily activating genes encoding cyclooxygenase-2. Rebamipide is used in a number of Asian countries including Japan (marketed as Mucosta), South Korea, China, and India (where it is marketed under the trade name Rebagen). It is not approved by the Food and Drug Administration for use in the United States. Studies have shown that rebamipide can fight the damaging effects of NSAIDs on the GIT mucosa.

Acadesine, also known as 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, AICA-riboside, and AICAR, is an AMP-activated protein kinase activator which is used for the treatment of acute lymphoblastic leukemia (ALL) and may have applications in treating other disorders such as mantle cell lymphoma (MCL). The mechanism by which acadesine selectively kills B-cells is not yet fully elucidated. The action of acadesine does not require the tumour suppressor protein p53 like other treatments. This is important, as p53 is often missing or defective in cancerous B-cells. Studies have shown acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Antiapoptotic proteins of the Bcl-2 family regulate MCL cell sensitivity to acadesine and combination of this agent with Bcl-2 inhibitors might be an interesting therapeutic option to treat MCL patients. Acadesine has anti-ischemic properties that is currently being studied (Phase 3) for the prevention of adverse cardiovascular outcomes in patients undergoing coronary artery bypass graft (CABG) surgery. Adenosine itself has many beneficial cardioprotective properties that may therefore be harnessed by this new class of drugs. Unlike adenosine, acadesine acts specifically at sites of ischemia and is therefore void of the systemic hemodynamic effects that may complicate adenosine therapy. Animal and in vitro studies have established acadesine as a promising new agent for attenuating ischemic and reperfusion damage to the myocardium. Acadesine also possesses the theoretical (but unproven) benefit of attenuating reperfusion injury after acute myocardial infarction (MI). Further research is needed to define the full potential of this unique agent in various clinical situations involving myocardial ischemia.