Bromocriptine is an ergot derivative with potent dopamine receptor agonist activity, which activates post-synaptic dopamine receptors. Bromocriptine is indicated for the treatment of dysfunctions associated with hyperprolactinemia. Bromocriptine therapy is indicated in the treatment of acromegaly and in the treatment of the signs and symptoms of idiopathic or postencephalitic Parkinson’s disease. It is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Some commonly reported adverse reactions include nausea, fatigue, dizziness, vomiting and headache. Bromocriptine may interact with dopamine antagonists, butyrophenones and certain other agents.

L-arginine is a nonessential amino acid that may play an important role in the treatment of cardiovascular disease due to its antiatherogenic, anti-ischemic, antiplatelet, and antithrombotic properties. It has been promoted as a growth stimulant and as a treatment for erectile dysfunction in men. L-arginine is a nonessential amino acid that may play an important role in the treatment of heart disease due to its block arterial plaque buildup, blood clots, platelet clumping, and to increase blood flow through the coronary artery. L-arginine is commonly sold as a health supplement claiming to improve vascular health and treat erectile dysfunction in men. L-arginine, which is promoted as a human growth stimulant, has also been used in bodybuilding. In the 1800s, it was first isolated from animal horn.

Arhalofenate is a uricosuric drug which lowers serum urate by blocking its reabsorption by the proximal tubules of the kidney. Arhalofenate activity is mediated by inhibition of URAT1, OAT4 and OAT10. Additionally, arhalofenate has been suggested to exert potent anti-inflammatory activity. Arhalofenate has completed Phase 2 and is ready to advance to Phase 3 as a novel potential treatment for gout. The drug was also tested in patients with type 2 diabetes mellitus (phase III study), where it demonstrated its ability to lower glucose level, acting as a selective, partial PPAR-gamma agonist. However, the development of arhalofenate as an anti-diabetic drug was terminated.

Talibegron (ZD2079) is a β3 adrenoceptor agonist and insulin sensitiser. It was developed as a potential treatment for obesity and non-insulin-dependent diabetes mellitus. Talibegron hydrochloride had been in phase II clinical trials by AstraZeneca for the treatment of type 2 diabetes and obesity. However, this research has been discontinued.

Aleglitazar is a dual agonist of PPARalpha/PPARgamma which was developed by Hoffmann-La Roche for the treatment of type 2 diabetes. Aleglitazar activates PPAR receptors with EC50 in nanomolar range and exerts a cardioprotective effect in vitro. The drug is currently in phase III of clinical trials.

Tagatose is a functional sweetener. It is naturally occurring and often found in dairy products. Tagatose is similar in texture and sweetness to sucrose (table sugar) but with only 38% of the calories. It is approved for use as a food additive as a low-calorie sweetener. Only 15 - 20 % of Tagatose is absorbed in the small intestines and metabolized similarly to sucrose; the bulk of ingested tagatose is fermented in the colon by bacteria producing short chain fatty acids which are subsequently absorbed and metabolized by the body without affecting insulin levels. Tagatose is being investigated by Spherix for the treatment of obesity and type II diabetes. Tagatose consumed orally significantly blunts the rise in plasma glucose seen after oral glucose in patients with diabetes mellitus in a dose-dependent manner without significantly affecting insulin levels. It has been suggested that Tagatose may act by attenuating the absorption of glucose in the intestines.

Mitoglitazone (previously known as MSDC-0160 or CAY-10415) is a mTOT (mitochondrial target of thiazolidinediones) modulator that targets the mitochondrial pyruvate carrier (MPC), which is a key controller of cellular metabolism. MSDC-0160 is modulated MPC and act as insulin sensitizers without activating PPAR gamma. (Mitoglitazone exhibits very low binding affinity and activity at PPARγ). Mitoglitazone has been used in trials phase II studying the treatment of Type 2 Diabetes and Alzheimer's disease; the treatment for diabetes was discontinued. In addition, MSDC-0160 has demonstrated significant neuroprotective effects in the En1+/- mouse model of Parkinson’s disease via modulation of the mTOR-autophagy signaling cascade.

NCX-4016, a nitric oxide non-steroidal anti-inflammatory drug (NO-NSAID) which can inhibit cyclooxygenase as well as release nitric oxide, is under development by NicOx as a potential treatment for thrombosis, inflammation and rheumatoid arthritis. NCX-4016 possesses a broad spectrum of antithrombotic and antiinflammatory activities. NCX-4016 has been shown to inhibit platelet activation in vitro more effectively than aspirin, to inhibit smooth muscle cell proliferation, to exert an endothelial cell protective activity and to suppress the function of several inflammatory cells potentially involved in atherothrombosis. In animal models, NCX-4016 protected from platelet thromboembolism, prevented restenosis in atherosclerosis-prone animals, protected the heart from ischemia/reperfusion injury, and induced neoangiogenesis in critically ischemic limbs. Moreover, it displayed little or no gastric toxicity and appeared to protect stomach from noxious stimuli, including aspirin. NCX-4016 has been evaluated in healthy volunteers and found to inhibit platelet cyclo-oxygenase-1 (COX-1) similarly to or slightly less than aspirin, to raise the circulating levels of NO-degradation products, and to have little or no gastric toxicity in short term studies. NCX-4016 was in Phase II clinical trials for the treatment of vascular disorders such as peripheral vascular disease and other cardiovascular diseases including thrombosis, complications of endothelium-related diseases such as diabetes and other. But this research was discontinued.

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is a lipid-lowering and antioxidant agent. It suppresses the development of hypercholesterolemic atherosclerosis in rabbits. Secoisolariciresinol diglucoside has been shown to have antioxidant and cardioprotective properties. SDG interferes with the development of different types of diseases like cardiovascular, diabetic, lupus nephritis, bone, kidney, menopause, reproduction, mental stress, immunity, atherosclerosis, hemopoietic, liver necrosis and urinary disorders due to its various biological properties including anti-inflammatory, antioxidant, antimutagenic, antimicrobial, antiobesity, antihypolipidemic and neuroprotective effects. Moreover, SDG has a defending mediator against various cancers by modulating multiple cell signaling pathways. The animal and human studies have shown the prevention role of SDG against some cancers (breast, lung and colon) as a result of its strong anti-proliferative, antioxidant, anti-oestrogenic and/or anti-angiogenic activity. It is proposed that the anticancer activity of SDG is associated with the inhibition of enzymes involved in carcinogenesis. Human studies showed the SDG as potential cardiovascular protector by mediating the mechanisms of total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerides and glucose metabolism. It was observed that 20 hypercholesterolaemia and hypertriglyceridaemia subjects receiving 600 mg SDG per day for 8 weeks led to significant reductions in total cholesterol, LDL-cholesterol and glucose concentrations compared with the placebo group. The animal and human studies revealed that high fat diet containing 0 · 5 to 1 · 0 % SDG reduces liver triglycerides content, serum triglycerides, total cholesterol, and insulin and leptin concentrations that resulted in significantly reduced visceral fat gain as compared to group of mice receiving high fat diet without SDG. SDG reduces C-reactive protein concentrations which are associated with insulin resistance and diabetes mellitus in type 2 diabetics. Daily consumption of low-fat muffin enriched with SDG (500 mg/day) for 6 week can reduce CRP concentrations. SDG has long acting hypotensive effect mediated through the guanylate cyclase enzyme.

Vaccenic acid (VA) (t11 octadecenoic acid) is a positional and geometric isomer of oleic acid (c9-octadecenoic acid), and is the predominant trans monoene in ruminant fats (50%–80% of total trans content). Dietary VA can be desaturated to cis-9,trans-11 conjugated linoleic acid (c9,t11-CLA) in ruminants, rodents, and humans. Hydrogenated plant oils are another source of VA in the diet, and it has been recently estimated that this source may contribute to about 13%–17% of total VA intake. In contrast to suggestions from the epidemiological studies, the majority of studies using cancer cell lines (Awad et al. 1995; Miller et al. 2003) or rodent tumors (Banni et al. 2001; Corl et al. 2003; Ip et al. 1999; Sauer et al. 2004) have demonstrated that VA reduces cell growth and (or) tumor metabolism. Animal and in vitro studies suggest that the anti-cancer properties of VA are due, in part, to the in vivo conversion of VA to c9,t11-CLA. However, several additional mechanisms for the anti-cancer effects of VA have been proposed, including changes in phosphatidylinositol hydrolysis, reduced proliferation, increased apoptosis, and inhibition of fatty acid uptake. In conclusion, although the epidemiological evidence of VA intake and cancer risk suggests a positive relationship, this is not supported by the few animal studies that have been performed. The majority of the studies suggest that any health benefit of VA may be conferred by in vivo mammalian conversion of VA to c9,t11-CLA. VA acts as a partial agonist to both peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ in vitro, with similar affinity compared to commonly known PPAR agonists. Hypolipidemic and antihypertrophic bioactivity of VA is potentially mediated via PPAR-/-dependent pathways.