Pterostilbene is a stilbenoid isolated from blueberries and Pterocarpus marsupium[1]. Shows anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic and anti-obesity properties[1][4]. Pterostilbene blocks ROS production[3], also exhibits inhibitory activity against various free radicals such as DPPH, ABTS, hydroxyl, superoxide and hydrogen peroxide[4].
Nonivamide is a agonist, which exhibits 4d-EC50 value of 5.1 mg/L in static toxicity tests.
Olivetol is a naturally phenol found in lichens and produced by certain insects, acting as a competitive inhibitor of the cannabinoid receptors CB1 and CB2[3]. Olivetol also inhibits CYP2C19 and CYP2D6 activity, with IC50s of 15.3 μM, 7.21 μM and Kis of 2.71 μM, 2.87 μM, respectively[1][2].
L-Isoleucine is one of 20 proteinogenic amino acids. L-Isoleucine is an essential amino acid.
Epiandrosterone is a steroid hormone with weak androgenic activity. Epiandrosterone is naturally produced by the enzyme 5α-reductase from the adrenal hormone DHEA.
SDMA (Symmetric dimethylarginine) is an endogenous inhibitor of nitric oxide (NO) synthase activity.
Peimisine(Ebeiensine) is a steroidal alkaloid which is the major biologically active component in Bulbus Fritillariae; possess a variety of toxicological and pharmacological effects on humans.
2'-Hydroxyacetophenone is found in alcoholic beverages. 2'-Hydroxyacetophenone is present in tomato, cassia, fried beef, rum, whiskey, cocoa, coffee and black tea. 2'-Hydroxyacetophenone is a flavouring ingredient. Building block in chemical synthesis.
Notoginsenoside Ft1 is a saponin isolated from Panax notoginseng; stimulator of angiogenesis.IC50 value:Target: angiogenesis stimulatorin vitro: Ft1 increases translocalization of hypoxia-inducible factor-1α (HIF-1α) from cytoplasm to nuclei, where it binds to the vascular endothelial growth factor (VEGF) promoter, increasing the expression of VEGF mRNA and the subsequent secretion of the growth factor. Ft1 induces the activation of PI3K/AKT and Raf/MEK/ERK signaling pathways [1]. Among the saponins examined, Ft1 was the most potent procoagulant and induced dose-dependent platelet aggregation. Ft1 reduced plasma coagulation indexes, decreased tail bleeding time and increased thrombogenesis. Moreover, it potentiated ADP-induced platelet aggregation and increased cytosolic Ca(2+) accumulation, effects that were attenuated by clopidogrel. Ft1 binds to platelet P2Y12 receptors. The increase in intracellular Ca(2+) evoked by Ft1 in HEK293 cells overexpressing P2Y12 receptors could be blocked by ticagrelor [2]. Ft1 caused endothelium-dependent relaxations, which were abolished by l-NAME (inhibitor of nitric oxide synthases) and ODQ (inhibitor of soluble guanylyl cyclase). Ft1 increased the cGMP level in rat mesenteric arteries. GR and ER? were present in the endothelial layer and their antagonism by RU486 and PHTPP, respectively, inhibited Ft1-induced endothelium-dependent relaxations and phosphorylations of eNOS, Akt and ERK1/2 [3]. Ft1 showed the best inhibitory effect on cell proliferation of SH-SY5Y cells with IC50 of 45μM. Ft1 not only arrested the cell cycle at S, G2/M stages, but also promoted cell apoptosis. Ft1 up-regulated the protein expressions of cleaved caspase 3, phospho-p53, p21, and cyclin B1, but down-regulated that of Bcl-2. Moreover, Ft1 enhanced the phosphorylation of ERK1/2, JNK and p38 MAPK [4].in vivo: Ft1 promotes the formation of blood vessels in Matrigel plug and wound healing in mice [1].
6''-O-Malonylgenistin(Malonylgenistin) is an isoflavone derivative.
Rufinamide(E 2080; CGP 33101; RUF 331) is a new antiepileptic agent that differs structurally from other antiepileptic drugs and is approved as adjunctive therapy for Lennox-Gastaut syndrome (LGS).IC50 Value:Target: in vitro:in vivo: Rufinamide and amitriptyline alleviated injury-induced mechanical allodynia for 4 h (maximal effect: 0.10 ± 0.03 g (mean ± SD) to 1.99 ± 0.26 g for rufinamide and 0.25 ± 0.22 g to 1.92 ± 0.85 g for amitriptyline) in mice [1]. Oral rufinamide suppressed pentylenetetrazol-induced seizures in mice (ED(50) 45.8 mg/kg) but not rats, and was active against MES-induced tonic seizures in mice (ED(50) 23.9 mg/kg) and rats (ED(50) 6.1 mg/kg) [2]. Intraperitoneal rufinamide suppressed pentylenetetrazol-, bicuculline-, and picrotoxin-induced clonus in mice (ED(50) 54.0, 50.5, and 76.3 mg/kg, respectively).Clinical trial: Exploratory Study to Evaluate the Effect of SYN-111 (Rufinamide) in Patients With Generalized Anxiety Disorder (GAD). Phase 2
Adenosine monophosphate is a key cellular metabolite regulating energy homeostasis and signal transduction.
Adenosine is a nucleoside composed of a molecule of adenine attached to a ribose sugar molecule (ribofuranose) moiety via a β-N9-glycosidic bond.Target: Nucleoside antimetabolite/analogAdenosine plays an important role in biochemical processes, such as energy transfer — as adenosine triphosphate (ATP) and adenosine diphosphate (ADP) — as well as in signal transduction as cyclic adenosine monophosphate, cAMP. It is also an inhibitory neurotransmitter, believed to play a role in promoting sleep and suppressing arousal. Adenosine also plays a role in regulation of blood flow to various organs through vasodilation.Adenosine is an endogenous purine nucleoside that modulates many physiological processes. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes. Extracellular adenosine concentrations from normal cells are approximately 300 nM; however, in response to cellular damage (e.g. in inflammatory or ischemic tissue), these concentrations are quickly elevated (600–1,200 nM). Thus, in regard to stress or injury, the function of adenosine is primarily that of cytoprotection preventing tissue damage during instances of hypoxia, ischemia, and seizure activity. Activation of A2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory.
Alisol B is a potentially novel therapeutic compound for bone disorders by targeting the differentiation of osteoclasts as well as their functions.IC50 Value:Target:In vitro: The in vitro cultured human renal tubular epithelial HK-2 cells were intervened with 5 ng/mL transforming growth factor-beta (TGF-beta), 0.1 micromol C3a, and 0.1 micromol C3a + 10 micromol alisol B, respectively. Exogenous C3a could induce renal tubular EMT. Alisol B was capable of suppressing C3a induced EMT [1]. Alisol-B strongly inhibited RANKL-induced osteoclast formation when added during the early stage of cultures, suggesting that alisol-B acts on osteoclast precursors to inhibit RANKL/RANK signaling. Among the RANK signaling pathways, alisol-B inhibited the phosphorylation of JNK, which are upregulated in response to RANKL in bone marrow macrophages, alisol-B also inhibited RANKL-induced expression of NFATc1 and c-Fos, which are key transcription factors for osteoclastogenesis. In addition, alisol-B suppressed the pit-forming activity and disrupted the actin ring formation of mature osteoclasts [2]. Alisol B induced calcium mobilization from internal stores, leading to autophagy through the activation of the CaMKK-AMPK-mammalian target of rapamycin pathway. Moreover, the disruption of calcium homeostasis induces endoplasmic reticulum stress and unfolded protein responses in alisol B-treated cells, leading to apoptotic cell death. Finally, by computational virtual docking analysis and biochemical assays, it was showed that the molecular target of alisol B is the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase [3].In vivo:
Melatonin is a hormone made by the pineal gland that can activates melatonin receptor. Melatonin plays a role in sleep and possesses important antioxidative and anti-inflammatory properties.
Perindopril is a long-acting ACE inhibitor of which is used to treat high blood pressure, heart failure or stable coronary artery disease.Target: ACEPerindopril is a long-acting ACE inhibitor. It is used to treat high blood pressure, heart failure or stable coronary artery disease in form of perindopril arginine (trade names include Coversyl, Coversum) or perindopril erbumine (trade name Aceon). According to the Australian government's Pharmaceutical Benefits Scheme website, based on data provided to the Australian Department of Health and Aging by the manufacturer, perindopril arginine and perindopril erbumine are therapeutically equivalent and may be interchanged without differences in clinical effect. However the dose prescribed to achieve the same effect will differ due to different molecular weights for the two forms. Perindopril is one of the most prescribed inhibitors of angiotensin converting enzyme, has a large evidence base, which allows to use it in patients with hypertension, diabetes mellitus type 2, coronary heart disease and chronic heart failure. In this review, the author focused on the evidence of organoprotecting properties of perindopril that lie outside lowering blood pressure.
4',7-Dimethoxyisoflavone is isolated from the leaves of Albizzia lebbeck, which shows antifungal activity.
Adenosine 5'-diphosphate is a nucleoside diphosphate. Adenosine 5'-diphosphate is the product of ATP dephosphorylation by ATPases.
D-luciferin is the natural substrate of luciferases that catalyze the production of light in bioluminescent insects.
Paradol is a pungent phenolic substance found in ginger and other Zingiberaceae plants. Paradol is an effective inhibitor of tumor promotion in mouse skin carcinogenesis, binds to cyclooxygenase (COX)-2 active site.
Jionoside B1 is a phenylpropanoid isolated from herbs of Eriophyton wallichii.
HEX3 is a fragment of the adenoviral hexon. Hexon is the major capsid protein of adenovirion and is comprised of three identical polypeptide chains.
Pioglitazone is a potent and selective PPARγ agonist with high affinity binding to the PPARγ ligand-binding domain with EC50 of 0.93 and 0.99 μM for human and mouse PPARγ, respectively.
Isosilybin (Isosilybinin) is a flavonoid from milk thistle; inhibits CYP3A4 induction with an IC50 of 74 μM.
Nicotinamide is a form of vitamin B3 that plays essential roles in cell physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a substrate to a class of enzymes that catalyze non-redox reactions. Nicotinamide is an inhibitor of SIRT1.
Tannic acid is a novel hERG channel blocker with IC50 of 3.4 μM.
S-Allyl-L-cysteine, one of the organosulfur compounds found in AGE, possess various biological effects including neurotrophic activity, anti-cancer activity, anti-inflammatory activity.
Dihydrokavain is one of the six major kavalactones found in the kava plant; appears to contribute significantly to the anxiolytic effects of kava, based on a study in chicks.
Cycloastragenol, a natural tetracyclic triterpenoid, was first identified when screening Astragalus membranaceus extracts for active ingredients with antiaging properties. IC50 value:Target:In vitro: In the study of Cycloastragenolon the treatment of degenerative diseases, the result showed that first-pass intestinal metabolism of cycloastragenol might occur upon passage through the intestinal epithelium. Cycloastragenol underwent extensive metabolism in rat and human liver microsomes with only 17.4% and 8.2%, respectively, of the starting amount of Cycloastragenol remaining after 30 min of incubation [1]. The present study demonstrates that cycloastragenol stimulates telomerase activity and cell proliferation in human neonatal keratinocytes. In particular, cycloastragenol promotes scratch wound closure of human neonatal keratinocyte monolayers in vitro [3]. In vivo: Rats were treated with Cycloastragenol (40 mg·kg- 1·d- 1) for 7 days to induce hepatic microsomal enzyme. The result showed that compared with the control, cycloastragenol obviously activated CYP2E1, and remarkably inhibited CYP3A4 [2].