MJ-15 is a selective cannabinoid CB(1) receptor antagonist with a potency in obesity and dyslipidemia treatment. In receptor binding assays, MJ-15 displayed a high affinity for rat cannabinoid CB(1) receptor (Ki=27.2 pM, and IC50=118.9 pM), but a much lower affinity for rat cannabinoid CB(2) receptor (only 46% inhibition at 10 uM). In animal experiments, MJ15 promoted the small intestine peristalsis in ICR mice and inhibited food intake and body weight increase in diet-induced obesity (DIO) rat and mouse. 40 mg/kg MJ15 significantly reduced food intake at initial 2 weeks of treatment, prevented the increase of body weight and adipose by 46% and 28% respectively in DIO rats, and reduced body weight and adipose gain by 70% and 23% respectively in early onset obesity DIO mice after 4 weeks treatment. Dyslipidemia were ameliorated in both models.

Fucosterol (24-ethylidene cholesterol) is a sterol that can be isolated from algae, seaweed and diatoms. Fucosterol exhibits various biological therapeutics, including anticancer, antidiabetic, antioxidant, hepatoprotective, antihyperlipidemic, antifungal, antihistaminic, anticholinergic, antiadipogenic, antiphotodamaging, anti-osteoporotic, blood cholesterol reducing, blood vessel thrombosis preventive and butyrylcholinesterase inhibitory activities. Fucosterol showed higher antiplasmodial activity as compared to chloroquine. Fucosterol showed the increase in the anti-oxidant enzymes such as hepatic cytosolic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-px) activities in CCl4-intoxicated rats. Fucosterol inhibited adipogenesis of 3T3-L1 preadipocytes through modulation of FoxO signalling pathway. Fucosterol is a dual-LXR agonist. It is displayed moderate inhibitory activity against aldose reductase and PTP1B.

ASARININ, (+)- ((+)-episesamin), an abundant lignan in sesame seed, has been identified as an active principle in an aqueous extract of Lindera obtusiloba (Japanese Spicebush) with a strong anti-inflammatory potential. (+)-episesamin (ES) is known to block the TNF-α-induced mitogenic VSMC response. Protective effect of (+)-episesamin against PDGF-BB-induced activation of vascular smooth muscle cells is mediated by induction of haem oxygenase-1 and inhibition of mitogenic signalling. ES interferes with inflammation-associated VSMC activation and subsequent decreased proliferation and migration due to anti-oxidative properties and impaired activation of NF-ĸB, known contributors to atherogenesis. These results suggest ES as a complemental treatment of VSMC specific vascular diseases such as atherosclerosis. (+)-Episesamin inhibits adipogenesis and exerts anti-inflammatory effects in 3T3-L1 (pre)adipocytes by sustained Wnt signaling, down-regulation of PPARγ and induction of iNOS. (+)-episesamin seems to be the active drug in the L. obtusiloba extract being responsible for the inhibition of adipogenesis and, thus, should be evaluated as a novel potential complementary treatment for obesity.

(+)-DDMS (R-Didesmethylsibutramine , (R)-DDMS) is one of sibutramine active metabolites. Sibutramine is widely used in the treatment of obesity. Sibutramine acts by inhibiting the reuptake of serotonin and noradrenaline in synapses, thereby enhancing both satiety and energy expenditure. In preclinical models (R)-enantiomer of Didesmethylsibutramine was clearly more potent than the (S)-enantiomers and (R)-didesmethylsibutramine shows some activity in all tests. (S)-didesmethylsibutramine affected locomotor behavior and the Porsolt test but appeared to be completely inactive on food intake. R-Didesmethylsibutramine is more potent than sibutramine in depressing food intake and decreasing body weight, suggest that these enantioselective metabolites might be safer and more effective than sibutramine as potential therapies for obesity.

Capsanthin, the red xanthophyll pigment, is used as a food additive approved by the European Union (EU) under the name as E160c. The common names for E160c are paprika extract, capsanthin or capsorubin. Capsanthin shows potent anti-adipogenic, lipolytic and fatty acid burning activities due to its potent adrenoceptor-beta2-agonistic activity. It was revealed, that capsanthin was not a thermogenic substance that is why it may be a good candidate for the development of new bioactive agent effective as a new anti-obese or insulin sensitivity enhancing substance.

Arctiin, isolated from Forsythia suspensa has been reported to have anti-inflammatory, anti-oxidant, antibacterial, and antiviral effects in vitro. It has been found to act as agonist of the adiponectin receptor 1. Has a potential role in the treatment of obesity. Arctiin has being shown to have anticancer effects in animal research.

Syringic acid (SYRA) is a potential antioxidant used in traditional Chinese medicine and is an emerging nutraceutical. Current reports claim its potential anti-angiogenic, anti-glycating, anti-hyperglycaemic, neuroprotective, and memory-enhancing properties in various animal models. Syringic acid (SA) possesses anti-obesity, anti-inflammatory and anti-steatotic effects via the regulation of lipid metabolic and inflammatory genes. SA is likely to be a new natural therapeutic agent for obesity or non-alcoholic liver disease. Syringic acid reduces oxidative stress and axonal degeneration in rat sciatic nerve after ischemia/reperfusion injury. Syringic acid may play a role in the treatment of peripheral nerve injuries due to ischemia/reperfusion.

2-methyl-4,6-dinitrophenol (4,6-Dinitro-ortho-cresol, DNOC) is a yellow crystalline solid. DNOC is used agriculturally as a larvicide, ovicide and insecticide (against locusts and other insects) as well as a potato haulm desiccant. It is also used as a polymerization inhibitor and as an intermediate in the chemical industry. For agricultural uses, DNOC is mainly formulated as emulsifiable concentrate, either aqueous or oily. 4,6-Dinitro-o-cresol is an uncoupler of the mitochondrial respiratory system. It causes an increase in basal metabolic rate with raised temperature and weight loss in man and animals. After metabolic activation, 4,6-dinitro-o-cresol has mutagenic potential in vitro. In vivo, evidence of clastogenic effects was obtained with a herbicide containing 4,6-dinitro-o-cresol but not with the pure substance. A long-term study with rats yielded no evidence of carcinogenic effects. During the 1930s, DNOC, along with dinitrophenol, was used therapeutically as a weight-loss agent after animal experiments had demonstrated that dinitrophenols increased the basal metabolic rate (BMR). The earliest mention of the use of these compounds for weight loss is a publication by Cutting and Tainter (1933) in which the authors reported clinical studies of dinitrophenol for this purpose. Dodds and Robertson (1933) reported that the related compound, DNOC, exhibited a greater effect on metabolism than dinitrophenol, leading to the marketing of DNOC for weight loss. Following the publication of these reports, dinitrophenol, and to a lesser extent, DNOC, began selling in drug stores and was prescribed by physicians for weight loss. DNOC acts mainly as an inhibitor of oxidative phosphorylation at the mitochondrial level, inducing a significant increase in basal metabolism and hyperthermy. The oxidation of carbohydrate forms the main source of energy of the body and the energy is “stored” in the form of compounds containing phosphate (high energy phosphate bonds of adenosine triphosphate or ATP). This compound is then a source of energy to the body. DNOC inhibits the formation of ATP. In the presence of DNOC the oxidative process continues and is even increased, but the energy cannot be converted to a useable form and it is therefore dissipated as heat. In muscle ATP cannot be re-synthesized and is progressively broken down to adenylic acid. The shortage of ATP may lead to muscular paralysis which for critical organs, such as heart and respiratory muscles, includes a blocking of their vital functions and in the case of death by DNOC poisoning, to early rigor mortis.

Jatrorrhizine is an active component of the traditional Chinese herb Coptis chinensis, which has been used to prevent and treat metabolic disorders. It is also found plants such as Enantia chlorantha, Thalictrum lucidumm, Thalictrum revolutum. Jatrorrhizine possesses antifungal, antibacterial activity. It has low toxicity and was studied in mouse models of obesity and hypercholesterolemia. The mechanism of action of Jatrorrhizine is not fully elucidated. The compound blocks alpha-1 and alpha-2 adrenoreceptors, monoamine oxidase A and B.

Formononetin, an isoflavone, derived from Astragalus membranaceus, possesses the potential to reduce obesity and associated metabolic disorders. Formononetin displays estrogenic properties and induces angiogenesis activities. It regulates adipocyte thermogenesis as a partial PPARγ agonist and produces proangiogenesis effects through estrogen receptor alpha (ERα)-enhanced ROCK-II signaling pathways, by direct binding to the ligand-binding domain (LBD) of ERα. Besides, was shown, that formononetin inhibits HMGB1 release by decreasing HMGB1 acetylation via upregulating SIRT1 in a PPARδ-dependent manner and the identification of this process may help to treat inflammation-related disorders.