t 4

L-Thyroxine (NSC 36397) is the major hormone derived from the thyroid gland. L-Thyroxine (NSC 36397) is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. L-Thyroxine (NSC 36397) is released from thyroglobulin by proteolysis and secreted into the blood. L-Thyroxine (NSC 36397) is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.

1-Octanol, a saturated fatty alcohol, functions as an inhibitor of T-type calcium channels (T-channels), showing an inhibitory concentration (IC50) of 4 μM for native T-currents[1]. Additionally, 1-Octanol is recognized for its potential as a biofuel, possessing diesel-like properties[2].

Thyroxine sulfate is a sulfoconjugated derivative of Thyroxine and is also a metabolite of Thyroxine.

1. Negletein (7-O-Methylbaicalein) has anti-inflammatory and immunomodulatory activities via inhibition of TNF-α, iNOS and IL-1β. 2. Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells. 3. Negletein shows a comparable redox-active potential, and it (50 μM, 4 h) can activate Nrf2. 4. Negletein shows significant antimicrobial activity. 5. Negletein has anti-hypoxia activity, it can significantly prolong the survival time of hypoxic mice.6. Negletein has anti- Alzheimer's disease activity, it inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. 7. Negletein (IC50: 3.89 + - 0.39 microM) exhibits potent inhibitory activity against nuclear factor of activated T cells (NFAT) transcription factor.

1. Lycobetaine (Ungeremine) is a potential biofungicide against Penicillium roqueforti and Aspergillus niger.2. Lycobetaine have strong antibacterial activity against Flavobacterium columnare . 3. Lycobetaine effectively targets mammalian as well as bacterial type I and type II topoisomerases.4. Lycobetaine shows strong acetylcholinesterase inhibitory activity(IC(50) value of 0.35 microM). 5. Lycobetaine has antiprotozoal activity, it shows good activity in in vitro assays against Trypanosoma brucei rhodesiense, T. cruzi.

1. Crebanine iv 5mg/kg can eonvert BaCl_2-induced arrhythmia into sinus rhythm in rats, and can significantly increase the tolerant dose of aconitine to produce ventrieular fibrillation(VF) and cardiac arrest (CA) in rata. 2. Crebanine can also decrease t

α-D-Glucose-1,6-bisphosphate is abis-phosphorylated derivative of α-D-glucose that has roles in carbohydrate metabolism.1It is the product of the reaction of glucose-1- or 6-phosphate with glucose-1,6-bisphosphate synthase (PGM2LI) in the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate.2It is also a cofactor for the bacterial enzyme phosphopentomutase.3,4α-D-Glucose-1,6-bisphosphate has been used in the study of carbohydrate metabolism. 1.Beitner, R.Regulation of carbohydrate metabolism by glucose 1,6-bisphosphate in extrahepatic tissues; comparison with fructose 2,6-bisphosphateInt. J. Biochem.22(6)553-557(1990) 2.Maliekal, P., Sokolova, T., Vertommen, D., et al.Molecular identification of mammalian phosphopentomutase and glucose-1,6-bisphosphate synthase, two members of the α-D-phosphohexomutase familyJ. Biol. Chem.282(44)31844-31851(2007) 3.Moustafa, H.M.A., Zaghloul, T.I., and Zhang, Y.-H.P.A simple assay for determining activities of phosphopentomutase from a hyperthermophilic bacterium Thermotoga maritimaAnal. Biochem.50175-81(2016) 4.Panosian, T.D., Nannemann, D.P., Watkins, G.R., et al.Bacillus cereus phosphopentomutase is an alkaline phosphatase family member that exhibits an altered entry point into the catalytic cycleJ. Biol. Chem.286(10)8043-8054(2011)

Phosphatidylserine is a naturally occurring phospholipid that comprises 2-10% of total phospholipids in mammals and is enriched in the central nervous system, particularly the retina. It is anionic and found mainly on the inner leaflet of the cell membrane. It is biosynthesized from phosphatidylcholine or phosphatidylethanolamine by phosphatidyl synthase 1 (PSS1) or PSS2, respectively, in the endoplasmic reticulum and can be reversibly converted back by the same enzymes. It can also be irreversibly converted to phosphatidylethanolamine by phosphatidylserine decarboxylase in the mitochondria. Phosphatidylserine binds to T cell immunoglobulin mucin type 1 (TIM-1) and TIM-4 receptors as well as brain-specific angiogenesis inhibitor 1 (BAI1), leading to anti-inflammatory and anti-atherosclerotic effects. It is also a cofactor involved in the activation of various signaling pathways through activation of protein kinase C, neutral sphingomyelinase, and c-Raf-1 protein kinase among others. Phosphatidylserine is externalized during apoptosis by scramblases in the plasma membrane as a signal for phagocytes to engulf the cell. Phosphatidylserines (bovine) is a mixture of bovine phosphatidylserines containing fatty acids with variable chain lengths at the sn-1 and sn-2 positions.

Xanthoquinodin A1 is a fungal metabolite that has been found inHumicolaand has diverse biological activities.1,2It inhibitsE. tenellaschizont formation in BHK-21 cells with a minimum effective concentration (MEC) value of 0.02 μg/ml.1Xanthoquinodin A1 is active againstB. subtilis,M. luteus,S. aureus,A. laidlawii, andB. fragilisin a disc assay when used at a concentration of 1 mg/ml. It is also active againstB. cereus(MIC = 0.44 μM).2Xanthoquinodin A1 is cytotoxic to KB, MCF-7, and NCI H187 cancer cells. 1.Tabata, N., Suzumura, Y., Tomoda, H., et al.Xanthoquinodins, new anticoccidial agents produced by Humicola sp. Production, isolation and physico-chemical and biological propertiesJ. Antibiot. (Tokyo)46(5)749-755(1993) 2.Tantapakul, C., Promgool, T., Kanokmedhakul, K., et al.Bioactive xanthoquinodins and epipolythiodioxopiperazines from Chaetomium globosum 7s-1, an endophytic fungus isolated from Rhapis cochinchinensis (Lour.) MartNat. Prod. Res.34(4)494-502(2020)

Paraherquamide E is a fungal metabolite originally isolated from P. charlesii with anthelmintic and insecticidal activities. It is lethal to C. elegans [LD50 = 6 μg ml] and O. fasciatus [LD50 = 0.089 μg nymph]. Oral administration of paraherquamide E [0.5-4 mg kg] reduces T. colubriformis fecal egg count in gerbils.

Terpendole I is a fungal metabolite that has been found in A. yamanashiensis.1 It is a weak inhibitor of acyl-coenzyme A:cholesterol acyltransferase (ACAT; IC50 = 145 μM) and is active against the bacteria B. cereus and B. subtilis (MICs = 100 μg/ml for both) but not S. aureus, P. aeruginosa, or K. pneumoniae (MICs = >200 μg/ml for all) or the fungus C. albicans (MIC = 200 μg/ml).1,2 It is cytotoxic to HeLa cells with an IC50 value of 52.6 μM.3 |1. Tomoda, H., Tabata, N., Yang, D.-J., et al. Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. III. Production, isolation and structure elucidation of new components. J. Antibiot. (Tokyo) 48(8), 793-804 (1995).|2. Zhao, J.-C., Wang, Y.-L., Zhang, T.-Y., et al. Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural antimicrobial agents. Phytochemistry 148, 21-28 (2018).|3. Nagumo, Y., Motoyama, T., Hayashi, T., et al. Structure-activity relationships of terpendole E and its natural derivatives. ChemistrySelect 2(4), 1533-1536 (2017).

Cerebroside C is a fungal metabolite and glycosphingolipid that has been found in the rice pathogenic fungusM. grisea.1It induces production of the phytoalexin momilactone A when applied to wounded rice leaves, indicating that cerebroside C is an elicitor of the hypersensitive response in rice. Cerebroside C increases germination rate and reduces germination time in wheat seeds in a concentration-dependent manner at 4°C.2It also increases root length, fresh weight, and dry weight of wheat seedlings when used at a concentration of 20 μg/ml at 4°C, indicating increased chilling tolerance. 1.Koga, J., Yamuchi, T., Shimura, M., et al.Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexin accumulation in rice plantsJ. Biol. Chem.273(48)31985-31991(1998) 2.Li, H.-X., Xiao, Y., Cao, L.-L., et al.Cerebroside C increases tolerance to chilling injury and alters lipid composition in wheat rootsPLoS One8(9)e73380(2013)

4′-Hydroxy-2′-methylacetophenone, a red wine aroma compound isolated from the cv. Bobal grape variety, exhibits ciliate toxicity and inhibits T. pyriformis growth with an IC50 of 0.65 mM[1][2].

Isogarcinol is a natural polyisoprenylated benzophenone first isolated from plant species in the genus Garcinia. It has immunosuppressant actions, inhibiting the protein phosphatase calcineurin (IC50 = 36 μM) and suppressing the proliferation of T cells. Oral administration of isogarcinol in mice decreases delayed type hypersensitivity, prolongs graft survival in allogeneic skin transplants, suppresses inflammation in collagen-induced arthritis, and reduces clinical symptoms in experimental autoimmune encephalomyelitis. Isogarcinol inhibits the proliferation of HL-60 and PC-3 cancer cells (IC50s = 4 and 8 μg ml, respectively) through cell cycle arrest and apoptosis.

Geranylgeranyl Pyrophosphate triammonium (GGPP triammonium) is a metabolite involved in protein geranylgeranylation, modulating endothelial cell proliferation and apoptosis during mouse embryonic angiogenesis. GGPP triammonium amplifies T(reg) differentiation by increasing IL-2 expression, improving DSS-induced colitis, useful in cancer research.

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

PE(18:1(9Z) 0:0) is a naturally-occurring lysophospholipid and an analog of plasmalogen lysophosphatidylethanolamine. PE(18:1(9Z) 0:0) induces transient increases in intracellular calcium in PC12 rat neuronal cells in a concentration-dependent manner. PE(18:1(9Z) 0:0) increases the production of IL-4 and IL-2, but not IFN-γ. In mouse serum, PE(18:1(9Z) 0:0) (1 μg animal) induces the T helper 2 response. PE(18:1(9Z) 0:0) levels increase in interscapular brown adipose tissue in mice following three-day cold exposure.

Stephacidin B is a fungal metabolite that has been found inA. ochraceus.1Dimeric stephacidin B is rapidly converted to a monomer, avrainvillamide ,in vitro.2Stephacidin B is cytotoxic to a variety of cancer cells, including testosterone-independent PC3 and -sensitive LNCaP prostate cancer cells (IC50s = 0.37 and 0.06 μM, respectively) and estradiol-independent SK-BR-3 and -sensitive MCF-7 breast cancer cells (IC50s = 0.32 and 0.27 μM, respectively).1It induces apoptosis in HepG2 and Huh7 hepatocellular carcinoma cells when used at a concentration of 4 μM.3 1.Qian-Cutrone, J., Huang, S., Shu, Y.-Z., et al.Stephacidin A and B: Two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cellsJ. Am. Chem. Soc.124(49)14556-14557(2002) 2.Wulff, J.E., Herzon, S.B., Siegrist, R., et al.Evidence for the rapid conversion of stephacidin B into the electrophilic monomer avrainvillamide in cell cultureJ. Am. Chem. Soc.129(16)4898-4899(2007) 3.Hu, L., Zhang, T., Liu, D., et al.Notoamide-type alkaloid induced apoptosis and autophagy via a P38/JNK signaling pathway in hepatocellular carcinoma cellsRSC Adv.9(34)19855-19868(2019)

Aspergillimide is a fungal metabolite originally isolated from A. japonicus.1 It reduces nicotinic acetylcholine receptor (nAChR) peak and slowly-desensitizing amplitudes induced by acetylcholine in silkworm (B. mori) larval neurons (IC50s = 20.2 and 39.6 nM, respectively) but has no effect on chicken α3β4-, α4β2-, and α7-containing nAChRs.2 Dietary administration of aspergillimide A (10 μg/g of diet) induces paralysis in silkworm fourth instar larvae.1 Aspergillimide A (10 and 20 mg/kg) reduces T. colubriformis fecal egg count in gerbils.3References1. Hayashi, H., Nishimoto, Y., Akiyama, K., et al. New paralytic alkaloids, asperparalines A, B and C, from Aspergillus japonicus JV-23. Biosci. Biotechnol. Biochem. 64(1), 111-115 (2000).2. Hirata, K., Kataoka, S., Furutani, S., et al. A fungal metabolite asperparaline a strongly and selectively blocks insect nicotinic acetylcholine receptors: The first report on the mode of action. PLoS One 6(4), e18354 (2011).3. Banks, R.M., Blanchflower, S.E., Everett, J.R., et al. Novel anthelmintic metabolites from an Aspergillus species; the aspergillimides. J. Antibiot. (Tokyo) 50(10), 840-846 (1997). Aspergillimide is a fungal metabolite originally isolated from A. japonicus.1 It reduces nicotinic acetylcholine receptor (nAChR) peak and slowly-desensitizing amplitudes induced by acetylcholine in silkworm (B. mori) larval neurons (IC50s = 20.2 and 39.6 nM, respectively) but has no effect on chicken α3β4-, α4β2-, and α7-containing nAChRs.2 Dietary administration of aspergillimide A (10 μg/g of diet) induces paralysis in silkworm fourth instar larvae.1 Aspergillimide A (10 and 20 mg/kg) reduces T. colubriformis fecal egg count in gerbils.3 References1. Hayashi, H., Nishimoto, Y., Akiyama, K., et al. New paralytic alkaloids, asperparalines A, B and C, from Aspergillus japonicus JV-23. Biosci. Biotechnol. Biochem. 64(1), 111-115 (2000).2. Hirata, K., Kataoka, S., Furutani, S., et al. A fungal metabolite asperparaline a strongly and selectively blocks insect nicotinic acetylcholine receptors: The first report on the mode of action. PLoS One 6(4), e18354 (2011).3. Banks, R.M., Blanchflower, S.E., Everett, J.R., et al. Novel anthelmintic metabolites from an Aspergillus species; the aspergillimides. J. Antibiot. (Tokyo) 50(10), 840-846 (1997).

1, 2, 3, 4, 6-Pentagalloylglucose (Penta-O-galloyl-β-D-glucose) and gallic acid from Pistacia lentiscus have antimutagenic and antioxidant activities. 2. 1, 2, 3, 4, 6-Penta-O-galloyl-beta-D-glucose (PGG) possesses potent anti-proliferative and anti-invasive effects, it also has inhibition of inducible nitric oxide synthase and cyclooxygenase-2 activity. 3. PGG may serve as a model for the development of new types of anti-diabetic and anti-metabolic syndrome therapeutics. 4. 1, 2, 3, 4, 6-Penta- O -galloyl-β- d -glucose has vasodilatory and anti-inflammatory effects, it dilates vascular smooth muscle and suppresses the vascular inflammatory process via endothelium-dependent nitric oxide (NO)/cGMP signaling. 5. 1, 2, 3, 4, 6-Penta-O-galloyl-beta-D-glucose can decrease the level of extracellular hepatitis B virus (HBV) (IC5, 1. microg/ml) in a dose-dependent manner, it also can reduce the HBsAg level by 25% at a concentration of 4 microg/ml; the gallate structure of PGG may play a critical role in the inhibition of anti-HBV activity, suggests that PGG could be a candidate for developing an anti-HBV agent. 6. 1, 2, 3, 4, 6-Penta-O-galloyl-β-D-glucose has anti-parasitic activity, displays an EC5 value of 67 μM, at least 6.6-fold more effective than the standard drug benznidazole against trypomastigote forms of T. cruzi.

(25R)-Spirost-4-ene-3,6,12-trione is a naturally occurring compound isolated from *Tribulus terrestris* L. [1].

3'4'7-Trihydroxyflavone can markedly inhibit the receptor activator of nuclear factor kappa B ligand (RANKL) induced osteoclastic differentiation from mouse bone marrow derived macrophages (BMMs), it inhibits osteoclastogenesis via nuclear factor of activ

Nervogenic acid has antioxidative, pro-coagulant, and antibacterial activities, it exhibits higher activity than that of t-butyl-4- hydroxyanisole (BHA) using the ferric thiocyanate method.