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.

CX 516, a compound synthesized by Cortex Pharmaceuticals using Ampakine® technology licensed from the University of California, was in clinical investigations for the treatment of Alzheimer's disease, schizophrenia, fragile X syndrome and autism, and sleep disorders, however, development of this drug candidate has been discontinued. CX 516 had an extremely short halflife in humans, very low potency and failed to show any benefits in phase II studies. The compound did have a good safety profile, reducing concerns about the toxicity of excess glutamate. Cortex subsequently terminated clinical development of CX 516.

Dehydroergosterol (DHE) is a naturally occurring, fluorescent analog of cholesterol that mimics the properties of cholesterol in cell membranes. It is readily bound by cholesterol-binding proteins and has been used for real-time probing of the sterol environment and to elucidate intracellular sterol trafficking in living organisms. Also was found, that DHE might be helpful in slowing down the deterioration in brain function by inducing a suitable microglial phenotype and might be a valuable preventive tool for dementia. DHE is considered safe to consume and is present in various dairy products, such as camembert cheese.

Harmaline is a fluorescent psychoactive indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is a partially hydrogenated form of harmine. Harmaline is produced by various plants including Peganum harmala aswell as Banisteriopsis caapi. Harmaline has been investigated as an anti-cancer agent and for the treatment of dementia in rats. However, Harmaline is known to induce tremors in rats.

Dihydroergocristine is an ergot alkaloid that has an partial agonist activity on dopaminergic and alpha-adrenergic receptors and antagonist activity on serotonin receptors. The drug was approved by FDA in combination with other alkaloids (dihydroergocornine, dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine mesylate salts) under the name Hydergine for the treatment of dimentia and cerebrovascular insufficiency.

Dihydroergocornine is an ergot alkaloid, one of the three components of ergoloid (trade name Hydergine). Dihydroergocornine (as the component of Ergoloid mesylates) has been used to treat dementia and age-related cognitive impairment (such as in Alzheimer disease), as well as to aid in recovery after stroke. There is no specific evidence which clearly establishes the mechanism by which Hydergine® (ergoloid mesylates) preparations produce mental effects, nor is there conclusive evidence that the drug particularly affects cerebral arteriosclerosis or cerebrovascular insufficiency. Hydergine may stimulates dopaminergic and serotonergic receptors and blocks alpha-adrenoreceptors.

Dihydro-alpha-ergocryptine is an ergot alkaloid that has an agonist activity on D2 dopaminergic receptors and a partial agonist activity on D1 receptors. It also demonstrated antagonistic activity towards alpha-adrenergic receptors. The drug was approved by FDA in combination with other alkaloids (dihydroergocornine, dihydroergocristine and dihydro-beta-ergocryptine mesylate salts) under the name Hydergine for the treatment of dimentia and cerebrovascular insufficiency.

Isorhynchophylline is a plant alkaloid isolated from Uncaria species with therapeutic potential for cardiovascular and central nervous system diseases. The antihypertensive effect of isorhynchophylline was firstly observed in 1989, which was strongly linked to the traditional use of Uncaria species (Gouteng in Chinese). Isorhynchophylline and rhynchophylline were the main hypotensive constituents in Uncaria rhynchophylla. In rat isolated mesenteric arteries and tail artery, isorhynchophylline inhibited the increased infusion pressure induced by high K+ and norepinephrine in a concentration-dependent manner. The potency of isorhynchophylline and rhynchophylline was similar in mesenteric arteries, but in the tail artery, the effect of isorhynchophylline on high K+ induced infusion pressure increase was stronger than that of rhynchophylline, and there was a similar trend in the contractile response induced by norepinephrine. Isorhynchophylline also inhibited the hypertensive effect of angiotensin II. The results indicate that in small blood vessels of rat, isorhynchophylline can directly inhibit the contractile responses induced by several agonists. In vivo, ouabain and CaCl2 were used to establish experimental arrhythmic models in guinea pigs and rats. In vitro, the whole-cell patch-clamp technique was used to study the effect of isorhynchophylline on action potential duration and calcium channels in acutely isolated guinea pig and rat cardiomyocytes. Isorhynchophylline, infusion 0–16 mg/kg at a constant rate, dose-dependently decreased heart rate, prolonged sinus node recovery time, and PR, AH, HV intervals. Isorhynchophylline significantly inhibited the heart rate and atrioventricular conduction. These inhibitory effects of isorhynchophylline were partially antagonized by isoprenaline, but not by atropine. Isorhynchophylline inhibited the automaticity and contractile force of isolated guinea pig atrium in a concentration-dependent manner. Isorhynchophylline significantly depressed adrenaline-induced automaticity, and prolonged functional refractory period and decreased excitability. Furthermore, 10 μmol/L of isorhynchophylline reduced the effect of ouabain on the contractile force in the left atrium and significantly inhibited the response to paired stimulation. In anesthetized dogs, isorhynchophylline markedly reduced the tension-time index which indicated myocardial oxygen consumption. The result indicates that the decrease of myocardial oxygen consumption by isorhynchophylline would protect the heart against ischemia induced by hypertension. Isorhynchophylline showed a mild central depressive effect in mice. Isorhynchophylline significantly decreased locomotor activity after oral administration to mice. The depression of locomotor activity upon administration of the alkaloid appears to be due to mediating of the central dopaminergic system. Isorhynchophylline dose-dependently inhibited 5-hydroxytryptamine (5-HT)2A receptor-mediated head-twitch but not 5-HT1A receptor-mediated head-weaving responses evoked by 5-methoxy-N, N-dimethyltryptamine. Isorhynchophylline attenuated the in vitro ischemia-induced neuronal damage in a dose-dependent manner. Isorhynchophylline protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Pretreatment with isorhynchophylline significantly elevated cell viability, decreased the levels of intracellular reactive oxygen species and malondialdehyde, increased the level of glutathione, and stabilized mitochondrial membrane potential in β- amyloid(25–35)-induced neurotoxicity in rat pheochromocytoma cells. In unthoracotomized dogs, isorhynchophylline (5 mg/kg, iv) reduced the mean arterial pressure but did not affect renal blood flow. Isorhynchophylline did not block nictitating membrane contraction induced by stimulating collum sympathetic nerve and did not decrease blood pressure after injected in the cerebral ventricle.

Bifemelane is a psychotropic drug, was found to inhibit monoamine oxidase (MAO). It inhibited type A MAO (MAO-A) competitively and type B (MAO-B) noncompetitively and it was a more potent inhibitor of MAO-A than of MAO-B. Bifemelane is an antidepressant and cerebral activator that is used in Japan for the treatment of cerebral infarction patients with depressive symptoms, and in the treatment of senile dementia as well. It also appears to be useful in the treatment of glaucoma.

Nicergoline is a semisynthetic ergoline derivative that has been used as a cerebral vasodilator and in peripheral vascular disease. Nicergoline seems to have an action: (i) as an alpha1-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Nicergoline has been suggested to ameliorate cognitive deficits in cerebrovascular disease.