hif-α

1. Cinnamaldehyde (Cinnamic Aldehyde) has antipyretic activity. 2. Cinnamaldehyde is a sedative agent. 3. Cinnamaldehyde inhibits invasive capabilities of MDA-MB-435S cells was correlated with down-regulating the expression of miR-27a. 4. Cinnamaldehyde induces the generation of reactive oxygen species and exerts vasodilator and anticancer effects. 5. Cinnamaldehyde appears to be a promising candidate as an adjuvant in combination therapy with 5-fluorouracil (5-FU) and oxaliplatin (OXA), two chemotherapeutic agents used in CRC treatment. The possible mechanisms of its action may involve the regulation of drugmetabolizing genes. 6. Cinnamaldehyde plays a certain role in inhibiting the occurrence and progression of melanoma and its action mechanism may be manifested by inhibiting expression of VEGF and HIF-α, thus blood vessel simulation and formation of new blood vessels of melanoma cells, and growth of tumors accordingly.

Deferoxamine (Desferrioxamine B) is an iron chelator. Deferoxamine can be used to reduce the accumulation and deposition of iron in tissues. Deferoxamine can improve neurological dysfunction by inhibiting ferroptosis and neuroinflammation after traumatic brain injury. It has antioxidant, anti-proliferation and anti-tumor activities, and can induce the production of HIF-1α, apoptosis and autophagy in cancer cells. It can be used to treat acute iron toxicity and COVID-19 related diseases.

Glucosamine (Chitosamine) is a natural product. Glucosamine is used as a dietary supplement. Glucosamine has pharmacological effects on cartilage and chondrocytes in osteoarthritis when used externally. Glucosamine regulates sugar metabolism. Glucosamine reduces the activity of glucoskinase in pancreatic islet homogenate.

Citric acid trilithium salt tetrahydrate (Lithium citrate tribasic tetrahydrate) , the active component of Lithium, is a medicine used in the therapy of psychiatric disease. It has shown the effects of signaling pathways and metabolic in the brain based on the particular disease and clinical condition model. According to the reports, Citric acid trilithium salt tetrahydrate was used as a mood stabilizer when treating bipolar mood disorders (BD) and lower the risk of self-harm in BD patient. In addition,Citric acid trilithium salt tetrahydrate has been the choice drug in the therapy of acute manic episodes.Citric acid trilithium salt tetrahydrate also could dissolve uric acid crystals in urine achieved from patients with gout. Besides,Citric acid trilithium salt tetrahydrate have some dose-dependent side-effects. The the main side-effects of Lithium Citrate is the tendency to inhibit the prostatic acid phosphatase enzyme (PAP), which result in the accumulation of PAP.

Hydroxycitric acid tripotassium hydrate (Potassium citrate monohydrate) is the major active ingredient of Garcinia cambogia and a derivative of citric acid, which effectively inhibits stone formation and HIF, and has antioxidation, anti-inflammation, and anti-tumor effects. It also competitively inhibits ATP citrate lyase, offering weight loss benefits.

Chloramphenicol (Chloromycetin) is a broad-spectrum antibiotic that inhibits the biosynthesis of bacterial proteins. Chloramphenicol acts primarily on the 50S subunit of the bacterial 70S ribosome and is active against peptidyltransferases, inhibiting the formation of peptide bonds.

2-Methoxyestradiol (2-ME2) is an orally bioavailable estradiol metabolite with potential antineoplastic activity. 2-Methoxyestradiol inhibits angiogenesis by reducing endothelial cell proliferation and inducing endothelial cell apoptosis. This agent also inhibits tumor cell growth by binding to tubulin, resulting in antimitotic activity, and by inducing caspase activation, resulting in cell cycle arrest in the G2 phase, DNA fragmentation, and apoptosis.

Chlorogenic acid is a natural phenol found in honeysuckle. Chlorogenic acid has a wide range of biological activities including anti-inflammatory, antioxidant, antitumor, antimicrobial, and neuroprotective.

Glucosamine hydrochloride (Chitosamine hydrochloride) is commonly used as a treatment for osteoarthritis, although its acceptance as a medical therapy varies.

Ethyl 3,4-dihydroxybenzoate (EDHB): a prolyl hydroxylase inhibitor attenuates acute hypobaric hypoxia mediated vascular leakage in brain.

(±)-Evodiamine is an alkaloid isolated from Evodiae fructus and a topoisomerase I inhibitor. It also inhibits adipocyte differentiation and diabetes by downregulating IGF-1/HIF-1α and IL-6/STAT pathways. As an inhibitor of NF-κB activation, it suppresses invasion, promotes apoptosis, and inhibits TNF-induced Akt activation.

Velutin shows the strongest inhibitory effect in NF-κB activation and exhibits the greatest effects in blocking the degradation of inhibitor of NF-κB as well as in inhibiting mitogen-activated protein kinase p38 and JNK phosphorylation. Velutin has anti-inflammatory property. Velutin exhibits the greatest potency among all flavones which reduce TNF-α and IL-6 production.

Clematichinenoside AR exerts anti-inflammatory and immunosuppressive properties, it has anti-arthritic effects on PI3K/Akt signaling pathway and TNF-α± associated with collagen-induced arthritis.

Acetylarenobufagin is a steroidal hypoxia-inducible factor-1 (HIF-1) modulator.

Oligomycin is a macrolide antibiotic produced by Streptomyces. Oligomycin is commonly used to study mitochondrial function and cellular energy metabolism and has antifungal and antitumor activities.

Panaxadiol (20(R)-Panaxadiol) is a novel antitumor agent extracted from the Chinese medicinal herb Panax ginseng.

Gramicidin A is a peptide antibiotic isolated from B. brevis.Gramicidin A is a highly hydrophobic channel-forming ion carrier that forms monovalent cation-permeable channels in artificial membranes.Gramicidin A induces the degradation of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and reduces the growth of a mouse xenograft model of human renal cell carcinoma. Gramicidin A has antibacterial, antimalarial and hemolytic activities.

1. β,β-Dimethylacrylshikonin (Dimethylacrylshikonin) is a promising agent for developing an improved strategy for radiotherapy against tumors. (a) Injection of Dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. (b) Dimethylacrylshikonin significantly suppressed the growth of H(22) transplantable hepatoma, and induced the activation of caspase-3 . (c) Dimethylacrylshikonin inhibited growth of gastric cancer SGC-791 cells by inducing ERK signaling pathway. 2. Dimethylacrylshikonin inhibits the proliferation of MCF-7 cells in vitro by inducing apoptosis through the downregulation of Bcl-2, upregulation of Bax and partial inactivation of the NF-κB pathway.

25(R,S)-Ruscogenin is a natual product.

1. Deoxyshikonin (Arnebin 7) may be a new drug candidate for wound healing and treatment of lymphatic diseases. 2. Deoxyshikonin enhances the ability of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) to undergo time-dependent in vitro cord formation. 3. Deoxyshikonin and dodecyl gallate show significantly synergic antimicrobial activity with penicillin in vivo and in vitro, and can effectively reduce nasopharyngeal and lung colonization caused by different penicillin-resistant pneumococcal serotypes.

1. Fraxinellone significantly reduced weight loss and diarrhea in mice and alleviated the macroscopic and microscopic signs of the disease. 2. Fraxinellone exhibited a variety of insecticidal activities including feeding-deterrent activity, inhibition of growth, and larvicidal activity. 3. Fraxinellone has effect in the midgut metabolism of Mythimna separata (M. separata), via protease (especially the weak alkaline trypsin-like enzyme), carboxylesterase and glutathione S-transferase.

1. Oroxylin A (Baicalein 6-methyl ether) has various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion. 2. Oroxylin A possesses abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP/LIP/CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS. 3. Oroxylin A inhibits UCP2s triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells; uncoupling protein 2 plays a key role in mitochondrial apoptotic pathway. 4. Oroxylin A inhibits N1ICD translocating to the nucleus and binding to epithelial-mesenchymal transition-related transcription factor Snail, thus suppressing the invasion and migration of MCF-7 cells. 5. Oroxylin A improves the sensitivity of K562/ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K/Akt/NF-κB pathway, and probably served as a most promising agent for CML treatment.

Dencichine (ODAP) is a neurotoxic agent. Dencichine is a haemostatic agent, the hemostatic effect relates to modulation of the coagulation system, platelet aggregation and fibrinolytic system. It has renoprotective effect, it could significantly prevent the progression of diabetic nephropathy possibly attribute to down-regulation of the TGF-β Smad pathway and rebalance the deposition and degradation of ECM proteins.

Cephaeline was highly active against protected primary CLL cells (relative IC50's 35nM ) and acted by repressing HIF-1α± and disturbing intracellular redox homeostasis.