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CAS No. :	30462-35-2
Formula :	C₄₃H₃₂O₂₀
M.W :	868.70
SMILES Code :	O=C(C1=CC(O)=C(O)C(O)=C1)O[C@H]2[C@H](OC3=CC(O)=CC(O)=C3C2)C4=C5C(C(C(O)=CC([C@@H]6[C@@H](CC7=C(O)C=C(O)C=C7O6)OC(C8=CC(O)=C(O)C(O)=C8)=O)=C5)=O)=C(O)C(O)=C4
Synonyms :	TF-3; ZP10; TFDG
MDL No. :	MFCD06797365

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338

A549 cells	75 µM	1 hour	To evaluate the antiviral activity of theaflavins against HSV-1, results showed that TF3 at 50 μM and above inhibited >99% of HSV-1 viral particle production.	Antiviral Res. 2015 Jun;118:56-67
Vero cells	75 µM	1 hour	To evaluate the antiviral activity of theaflavins against HSV-1, results showed that TF3 at 50 μM and above inhibited >99% of HSV-1 viral particle production.	Antiviral Res. 2015 Jun;118:56-67
CV-1 cells	250-500 µM	1 hour	Assess the inactivation effect of TF-3 on HSV-1 clinical isolates. Results indicated that some HSV-1 clinical isolates required higher concentrations of TF-3 (250-500 μM) to achieve comparable inactivation to HSV-2.	Antimicrob Agents Chemother. 2013 Aug;57(8):3806-14
Vero cells	100 µM	1 hour	Evaluate the efficacy of TF-3 combined with lactic acid (LA) in inactivating HSV-1 and HSV-2 at various pH levels. Results showed that TF-3 combined with LA almost completely inactivated clinical isolates of HSV-2 and HSV-1 at pH 4.5 to 5.7.	Antimicrob Agents Chemother. 2013 Aug;57(8):3806-14
3T3-L1 adipocytes	3.14 µM, 6.25 µM, 12.5 µM, 25 µM, 50 µM, 100 µM	10 days (Day 18 to Day 28)	Theaflavin-3,3'-digallate (TF-3) reduced the impact of methylmercury by maintaining the adipocytes morphology and secretion patterns of adiponectin, resistin and 4-hydroxynonenal. TF-3 showed dose-dependent effects in counteracting methylmercury-induced oxidative stress and inflammation.	Int J Mol Sci. 2019 Jun 5;20(11):2755
H9c2 cells	1-10 µM	24 hours	Prevention of angiotensin II-induced pathological cardiac hypertrophy via inhibition of the CaN-NFAT signaling pathway	Nutrients. 2022 Mar 26;14(7):1391
Peritoneal macrophages	40 µM	24 hours	To evaluate the inhibitory effect of TFDG on NO production in LPS-activated macrophages. Results showed that TFDG downregulated NO production in a concentration-dependent manner, with maximal effect at 40 μM and no cytotoxicity observed.	Br J Pharmacol. 2006 Sep;149(1):121-31
Human ovarian carcinoma cells OVCAR-3	10-20 µM	24 hours	TF3 significantly reduced the viability of OVCAR-3 cells and induced apoptosis and G0/G1 cell cycle arrest.	Molecules. 2019 Feb 14;24(4):673
Demineralized dentin collagen	12.5, 25, 50, 100 mg/mL	30 and 60 seconds	TF3/ethanol solution could effectively crosslink demineralized dentin collagen and improve its resistance to collagenase digestion and biomechanical properties (p<0.05), showing concentration and time dependence. The effect of 25 and 50 mg/ml TF3/ethanol solution was similar to that of 5% GA, whereas the 100 mg/mL TF3/ethanol solution exhibited better performance (p<0.05).	Front Bioeng Biotechnol. 2024 May 15;12:1401032
Rat aortic rings	0.02–2 µM	30 minutes	To investigate the vasorelaxation induced by theaflavin-3,3'-digallate and its mechanism, it was found that it mediates NO-dependent vasodilation through the production of hydrogen peroxide (H2O2).	Antioxidants (Basel). 2020 May 7;9(5):390
Rat aortic endothelial cells (RAECs)	0.5 μg/mL	30 minutes	TF3 suppressed Hcy-induced ER stress markers (e.g., phosphorylated eIF2α, ATF3, and cleaved ATF6) and reduced ROS production.	Sci Rep. 2015 May 15;5:10340
Rat aortic smooth muscle cells (RASMCs)	1, 10, 20 µM	48 hours	To evaluate the effect of TF3 on PDGF-BB-induced migration in RASMCs. Wound healing and Transwell assays showed that TF3 inhibited PDGF-BB-induced migration in a concentration-dependent manner.	Front Pharmacol. 2022 Jul 12;13:861319
Rat aortic smooth muscle cells (RASMCs)	1, 10, 20 µM	48 hours	To evaluate the effect of TF3 on PDGF-BB-induced proliferation in RASMCs. EdU and CCK-8 assays showed that TF3 inhibited PDGF-BB-induced proliferation in a concentration-dependent manner.	Front Pharmacol. 2022 Jul 12;13:861319
Rat aortic smooth muscle cells (RASMCs)	1, 10, 20 µM	48 hours	To evaluate the effect of TF3 on PDGF-BB-induced phenotypic switching in RASMCs. Results showed that TF3 reversed the PDGF-BB-induced decrease in contractile proteins (MYH11, α-SMA, and SM22) in a concentration-dependent manner.	Front Pharmacol. 2022 Jul 12;13:861319
Purified F1-ATPase	0.7 µM	5 minutes	To evaluate the inhibitory effect of Theaflavin 3,3'-digallate on purified F1-ATPase, results showed an IC50 value of 0.7 μM and an inhibition rate of 90%.	J Nutr Biochem. 2012 Aug;23(8):953-60
E. coli membrane vesicles	10-20 µM	5 minutes	To evaluate the inhibitory effect of Theaflavin 3,3'-digallate on ATP hydrolysis, results showed an IC50 value of 10 μM and an inhibition rate of 90%.	J Nutr Biochem. 2012 Aug;23(8):953-60
MC3T3-E1 cells	0.1 µM and 1 µM	7 days	TFDG promotes the formation of osteoblasts and enhances their mineralization ability in inflammatory environment	Front Pharmacol. 2021 Mar 23;12:648969

Zebrafish (Danio rerio)	Alloxan-induced diabetic model	Water solution treatment	0.5-20 μg/mL	24 hours	To evaluate the hypoglycemic effect and mechanism of TF3 in diabetic zebrafish, results showed that TF3 could significantly reduce blood glucose levels by down-regulating PEPCK and up-regulating GCK expression, and promote β cells regeneration at low concentrations.	Nutrients. 2021 Dec 7;13(12):4379
C57BL/6 mice	Ovariectomy-induced osteoporosis model	Injection	1 mg/kg and 10 mg/kg	Every 2 days for 5 weeks	TFDG significantly increased bone mass in ovariectomized mice, reduced the release of proinflammatory cytokines, and increased the expression of osteogenic markers	Front Pharmacol. 2021 Mar 23;12:648969
DBA/1 mice	Collagen-induced arthritis (CIA) model	Intraperitoneal injection	1 mg/kg or 10 mg/kg	6 days a week for 8 weeks	To investigate the effect of TFDG on CIA mice. Results showed that TFDG ameliorated joint destruction, reduced inflammatory cytokines, and promoted M2 macrophage polarization.	J Inflamm Res. 2023 Jan 10;16:109-126
C57BL/6J female mice	Ovariectomy (OVX)-induced osteoporosis model	Intraperitoneal injection	1 mg/kg, 10 mg/kg	Three times per week for 3 months	To evaluate the effect of TF3 on OVX-induced bone loss. Results showed that TF3 significantly attenuated OVX-induced bone loss and osteoclastogenesis in a dose-dependent manner.	Front Pharmacol. 2020 Jun 29;11:803
C57BL/6 mice	Carotid artery ligation model	Intraperitoneal injection	10 mg/kg	Injected one day before surgery and repeated every other day for 14 or 28 days	To evaluate the effect of TF3 on carotid artery ligation-induced neointimal hyperplasia. Results showed that TF3 significantly reduced the intima-to-media ratio (I/M ratio) and increased lumen diameter and area.	Front Pharmacol. 2022 Jul 12;13:861319
Chicken embryos	Chick chorioallantoic membrane (CAM) model	Implanted onto the CAM	25 µM	Single administration, lasting for 5 days	To evaluate the inhibitory effect of TF3 on tumor angiogenesis in vivo, results showed that TF3 significantly reduced blood vessel density.	Int J Oncol. 2016 Jan;48(1):281-92
Mice	Leptin-deficient obese (ob/ob) mice	Intraperitoneal injection	5 mg/kg, 10 mg/kg, 20 mg/kg	Once daily for 4 weeks	TF3 treatment prevented body weight and waistline gain, reduced lipid accumulation, and alleviated liver function injury, as well as decreased serum lipid levels and TG levels in livers.	Front Pharmacol. 2022 Aug 29;13:925264
BALB/c mice	TNBS-induced colitis model	Oral gavage	5 mg/kg/day	Once daily for 18 days	To evaluate the protective effect of TFDG on TNBS-induced colitis. Results showed that TFDG significantly improved macroscopic and microscopic damage scores, reduced neutrophil infiltration, decreased mRNA and protein levels of proinflammatory cytokines (TNF-α, IL-12, IFN-γ) and iNOS, and preserved IκBα by inhibiting IKK activity and nuclear translocation of NF-κB.	Br J Pharmacol. 2006 Sep;149(1):121-31
BALB/c mice	S aureus pneumonia model	Hypodermic injection	50 mg/kg TFDG, 15 mg/kg cephalothin	Every 12 hours for 72 hours	Evaluate the protective effect of TFDG combined with cephalothin against S aureus pneumonia in mice, showing that the combination significantly reduced mortality and alleviated lung pathological changes.	J Cell Mol Med. 2019 Oct;23(10):6955-6964

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CAS No.: 30462-35-2

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CAS No.: 30462-35-2

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed