4-n-octylphenol is alkylphenol widely used as a surfactant. 4-n-octylphenol exposure was associated with idiopathic male infertility. Fetal exposure to the very weak estrogenicity of 4-n-octylphenol could enhance the induction of mammary carcinomas but not affect the induction of benign proliferative lesions. It is an endocrine-disrupting chemical. 4-n-octylphenol is an agonist and antagonist of estrogen receptor and androgen receptor, respectively. 4-n-octylphenol at high doses caused reduction in mammary tumor development in female human c-Ha-ras proto-oncogene transgenic rats and possibly non-transgenic rats.

Macelignan is a neuroprotective lingan isolated from nutmeg (Myristica fragrans) that protects dopaminergic neurons from inflammatory degeneration. Macelignans have been shown to possess a broad range of pharmacological properties, including anti-bacterial, antiinflammatory, and anti-cancer activity. It has also been demonstrated that macelignans have anti-diabetes, hepatoprotective, and more importantly, neuroprotective properties. Apparently, the neuroprotective effect of macelignan is mediated by PPARγ activation and arginase-1 expression. Macelignan inhibits LPS induced production of NO as well and inflammatory cytokines including TNF and IL- 1β in primary cultures of microglia. Macelignan reduced serum glucose, insulin, triglycerides, free fatty acid levels, and triglycerides levels in the skeletal muscle and liver of db/db mice. Furthermore, macelignan significantly improved glucose and insulin tolerance in these mice, and without altering food intake, their body weights were slightly reduced while weights of troglitazone-treated mice increased. Macelignan increased adiponectin expression in adipose tissue and serum, whereas the expression and serum levels of tumor necrosis factor-alpha and interleukin-6 decreased. Macelignan downregulated inflammatory gene expression in the liver and increased AMP-activated protein kinase activation in the skeletal muscle of db/db mice. Strikingly, macelignan reduced endoplasmic reticulum (ER) stress and c-Jun NH2-terminal kinase activation in the liver and adipose tissue of db/db mice and subsequently increased insulin signaling.

Capromorelin is a potent ghrelin receptor agonist. Capromorelin is indicated for appetite stimulation in dogs. Plasma insulin-like growth factor-I (IGF-I) was elevated progressively over a 5-d course of daily oral dosing in dogs. In healthy older adults at risk for functional decline, administration of the capromorelin may improve body composition and physical function. Adverse events included fatigue, insomnia, and small increases in fasting glucose, glycosylated hemoglobin, and indices of insulin resistance.

Trimethylamine (or TMA) a tertiary amine, is synthesized by the action of microbial enzymes in humans. The decrease of TMA metabolism and excessive TMA excretion cause the disease trimethylaminuria and some other diseases associated with the abnormal level of TMA, e.g., obesity, diabetes, cardiovascular diseases. It was shown, that TMS is a full agonist of human trace amine-associated receptor 5, TAAR5. In addition, TMA is a precursor of N-oxide form, an emergent biomarker of human health that can lead to renal diseases, neurological disorders, and cancer.

Alprostadil isopropyl ester induces a considerable and rapidly appearing increased negativity of interstitial fluid pressure in skin that will enhance edema formation. It is able to inhibit contraction of fibroblast-populated collagen gels, which depends on b1-integrin function. Taken together, Alprostadil isopropyl ester can modulate e interstitial fluid volume and interstitial fluid pressure through effects on the connective tissue cells and extracellular matrix components. Alprostadil isopropyl ester was a test compound in preclinical studies of a selective EP2 and EP4 prostanoid receptor agonists for the treatment of female sexual dysfunction.

SERINE, D- (D-serine) is a non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines and other amino acids. A considerable level of D-serine was discovered, surprisingly, in the mammalian brain in the early 1990s. Since then, D-serine has been considered to be a co-agonist of glutamate at the glycine site of NMDA receptors. D-serine plays an important role in the central nervous system as an endogenous ligand for the glycine site of glutamate N-Methyl-D-Aspartate (NMDA) receptors. D-serine is synthetized by racemization of L-serine in most neural and non-neural cells, and modulates a variety of physiological functions in mammals. D-Serine synthesis is attributed to Serine Racemase (SR), which catalyses the synthesis of D-serine from L-serine. D-serine may play a role in the pathophysiology of neuropsychiatric disorders, such as schizophrenia, which may be linked to NMDA receptor hypo-function. Studies in genetic and pharmacological animal models with decreased D-serine levels have shown that these animals displayed behavioural abnormalities similar to those seen in schizophrenia. Moreover, exogenous administration of D-serine and related compounds improved several phenotypes relevant to schizophrenia, which could have positive clinical implications in humans. The results of a clinical trial in Taiwanese schizophrenic patients who received D-serine as adjuvant treatment indicated that those patients who received D-serine treatment, improved positive, negative and cognitive symptoms seen in schizophrenia. In addition, this clinical trial showed that D-serine did not worsen side effects from other antipsychotics, which may be due to its selective action at the NMDA-glycine site. Therefore, D-serine could be considered as a therapeutic approach for schizophrenia, which is different from the dopaminergic approach. It has also been shown that exogenous d-serine administration can suppress appetite and alter food preference. Thus NMDA receptor and its co-agonist d-seine participate in the control of appetite and food preference, which can be used to suppress obesity. D-serine has been shown to have cognitive-enhancing properties in different brain disorders and in age-related cognitive decline. From a clinical perspective, it is important to highlight that in a recent double-blind placebo-controlled cross-over study our group observed that an acute oral administration of 30 mg/kg of d-serine improved spatial learning and problem solving. D-serine may be especially useful for depression because of its acute and chronic antidepressant effects,

Estriol (E3), also spelled oestriol, is a steroid, a weak agonist of the estrogen receptors ERα and ERβ., and a minor female sex hormone. According to in vitro study, the relative binding affinity (RBA) of estriol for the human ERα and ERβ was 11.3% and 17.6% of that estradiol, respectively, and the relative transactivational capacity of estrone at the ERα and ERβ was 10.6% and 16.6% of that of estradiol, respectively. Estriol is marketed widely in Europe and elsewhere throughout the world under the brand names Ovestin, Ortho-Gynest, and a variety of others. It is available in oral tablet, vaginal cream, and vaginal suppository form, and is used in menopausal hormone therapy for the treatment of menopausal symptoms. Estriol is also available in some countries as estriol succinate (brand name Synapause), a dosage-equivalent ester prodrug of estriol. Estriol and estriol succinate are not approved for use in the United States and Canada, although they have been produced and sold by compounding pharmacies in North America for use as a component of bioidentical hormone therapy. Estriol can be measured in maternal blood or urine and can be used as a marker of fetal health and well-being. If levels of unconjugated estriol (uE3 or free estriol) are abnormally low in a pregnant woman, this may indicate chromosomal or congenital anomalies like Down syndrome or Edward's syndrome. It is included as part of the triple test and quadruple test for antenatal screening for fetal anomalies.

Zeranol is a non-steroidal anabolic growth promoter with potent estrogenic activity that is widely used as a growth promoter in the US beef industry. It is a mycotoxin, derived from fungi in the Fusarium family, it is an estrogen agonist. Zeranol is approved for use as a growth promoter in livestock, including beef cattle, in the United States. In Canada, it is approved for use in beef cattle only. Zeranol was officially banned in Europe due to safety concerns because of its potential carcinogenic and endocrine-disrupting biological activity. Merck Animal Health markets zeranol under the brand name Ralgro. It has being shown, that zeranol may increase cancer cell proliferation in already existing breast cancer.

Tocopheryl retinoate (tocoretinate) is an alpha-tocopherol ester of all-trans retinoic acid (ATRA) and safely used to treat skin ulcers. Tocopheryl retinoate stimulates the formation of granulation tissue in the ulcer, and enhances the migration of guinea pig macrophages and stimulates the proliferation of human skin fibroblasts. It is usually used to treat pressure ulcer (bedsore) and skin ulcer (burn ulcer, diabetic ulcer, leg ulcer). Topical application of tocoretinate reduced the clinical symptoms of lichen amyloidosis and macular amyloidosis, and normalized disturbed epidermal differentiation.