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CAS No. :	478-43-3
Formula :	C₁₅H₈O₆
M.W :	284.22
SMILES Code :	O=C(C(C=C1C2=O)=CC(O)=C1C(C3=C2C=CC=C3O)=O)O
Synonyms :	Rheic Acid; Rhubarb yellow; Rheinic Acid
MDL No. :	MFCD00009618
InChI Key :	FCDLCPWAQCPTKC-UHFFFAOYSA-N
Pubchem ID :	10168

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Staphylococcus xylosus	64 μg/mL (MIC)	16 hours	Determine the minimum inhibitory concentration (MIC) of Rhein against S. xylosus, results showed that the MIC of Rhein was 64 μg/mL.	Curr Res Food Sci. 2024 Mar 16;8:100718
CCD-18Co	0, 10, 20, 40, 60 µM	24 hours	To evaluate the effect of Rhein on normal colon fibroblast CCD-18Co cells. Results showed that Rhein had no significant effect on the viability of CCD-18Co cells.	Cancers (Basel). 2021 Apr 30;13(9):2176
NCM-460 cells	8 µM and 16 µM	24 hours	To detect the effect of Rhein on uric acid production, results showed that Rhein treatment did not significantly alter uric acid concentration or XDH expression.	Theranostics. 2020 Aug 29;10(23):10665-10679
Staphylococcus xylosus	1/2, 1/4, 1/8, and 1/16 MIC	24 hours	Investigate the interference effect of Rhein on the biofilm formation of S. xylosus, results showed that sub-MIC concentrations of Rhein significantly interfered with biofilm formation.	Curr Res Food Sci. 2024 Mar 16;8:100718
HOMF cells	0, 25, 50, 100 µM	24 hours	To evaluate the effect of Rhein on normal oral epithelial cells. Results showed that Rhein had no significant effect on the proliferation of hOMF cells.	Int J Mol Sci. 2023 May 9;24(10):8507
Cardiac fibroblasts (CFs)	5 and 25 µM	24 hours	Rhein significantly suppressed Ang II-induced CF proliferation, migration, and collagen expression, and reduced ROS levels.	J Transl Med. 2022 Jul 6;20(1):305
Neonatal rat cardiomyocytes (CMs)	5 and 25 µM	24 hours	Rhein significantly attenuated Ang II-induced CM hypertrophy and ROS production, and restored antioxidase activity including SOD and GSH.	J Transl Med. 2022 Jul 6;20(1):305
RAW264.7 macrophages	5, 20 µM	24 hours	To evaluate the effect of rhein on the expression of NLRP3 and cleaved IL-1β in LPS + ATP-induced RAW264.7 macrophages. Results showed that rhein significantly reduced the expression of these proteins.	Drug Des Devel Ther. 2017 Jun 6;11:1663-1671
RAW264.7 macrophages	1, 5, 20 µM	24 hours	To evaluate the effect of rhein on NO production in LPS-induced RAW264.7 macrophages. Results showed that rhein significantly reduced NO production.	Drug Des Devel Ther. 2017 Jun 6;11:1663-1671
RAW264.7 macrophages	1, 5, 20 µM	24 hours	To evaluate the effect of rhein on the production of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) in LPS-induced RAW264.7 macrophages. Results showed that rhein significantly reduced the production of these cytokines.	Drug Des Devel Ther. 2017 Jun 6;11:1663-1671
Mouse blastocyst cells	5–20 µM	24 hours	Induced cell apoptosis, decreased inner cell mass cell numbers	Int J Mol Sci. 2017 Sep 20;18(9):2018.
AC16 cells	0, 30, 60, 120 µM	24 hours	To evaluate the inhibitory effect of Rhein on AngII-induced cardiomyocyte hypertrophy. Results showed that Rhein significantly reversed the upregulation of ANP, BNP, and β-MHC mRNA and protein expression induced by AngII.	Front Pharmacol. 2022 Aug 26;13:940574
H9C2 cells	0, 30, 60, 120 µM	24 hours	To evaluate the inhibitory effect of Rhein on AngII-induced cardiomyocyte hypertrophy. Results showed that Rhein significantly reversed the upregulation of ANP, BNP, and β-MHC mRNA and protein expression induced by AngII.	Front Pharmacol. 2022 Aug 26;13:940574
DLD1	0, 10, 20, 40, 60 µM	24, 48, 72 hours	To evaluate the effect of Rhein on DLD1 cell growth. Results showed that Rhein significantly inhibited the growth of DLD1 cells with an IC50 value of 46.51 µM.	Cancers (Basel). 2021 Apr 30;13(9):2176
HCT116	0, 10, 20, 40, 60 µM	24, 48, 72 hours	To evaluate the effect of Rhein on HCT116 cell growth. Results showed that Rhein significantly inhibited the growth of HCT116 cells with an IC50 value of 47.77 µM.	Cancers (Basel). 2021 Apr 30;13(9):2176
HCT15	0, 10, 20, 40, 60 µM	24, 48, 72 hours	To evaluate the effect of Rhein on HCT15 cell growth. Results showed that Rhein significantly inhibited the growth of HCT15 cells with an IC50 value of 41.25 µM.	Cancers (Basel). 2021 Apr 30;13(9):2176
HepaRG cells	50, 75, 100 µM	24, 48, 72 hours	To evaluate the cytotoxicity of rhein on HepaRG cells, results showed that rhein significantly inhibited cell viability and induced apoptosis.	Int J Mol Sci. 2018 Apr 2;19(4):1060
AR42J cells	0.25, 0.5, 1 μg/ml	4 hours	To investigate the protective effects of Rhein on the cerulein-induced AR42J cell injury model. Results showed that Rhein significantly reduced amylase activity and TNF-α levels induced by cerulein, and inhibited the expression of JAK2/STAT3 signaling pathway-related proteins.	Front Pharmacol. 2022 Mar 17;13:778221
Ca9-22 cells	0, 25, 50, 100 µM	48 hours	To evaluate the effect of Rhein on the growth of oral cancer cells. Results showed that Rhein significantly inhibited the proliferation of Ca9-22 cells and induced apoptosis and S-phase cell cycle arrest.	Int J Mol Sci. 2023 May 9;24(10):8507
YD-10B cells	0, 25, 50, 100 µM	48 hours	To evaluate the effect of Rhein on the growth of oral cancer cells. Results showed that Rhein significantly inhibited the proliferation of YD-10B cells and induced apoptosis and S-phase cell cycle arrest.	Int J Mol Sci. 2023 May 9;24(10):8507
RAW264.7 cells	5 and 25 µM	48 hours	Rhein significantly reduced intracellular ROS levels, inhibited P65 activation, and thus suppressed M1 polarization of macrophages.	Inflamm Res. 2023 Jun;72(6):1237-1255
Primary islet cells	1 mg/mL	72 hours	To evaluate the effect of rhein on HG-induced apoptosis in primary islet cells. Results showed that rhein significantly reduced apoptosis and maintained insulin secretion function.	Diabetes. 2013 Nov;62(11):3927-35

Mice	Embryonic development model	Intravenous injection	1, 3, and 5 mg/kg/day	Once daily for four days	Induced apoptosis of blastocyst-stage embryos, early embryonic developmental injury, and decreased fetal weight	Int J Mol Sci. 2017 Sep 20;18(9):2018.
Zebrafish (Danio rerio)	Transgenic zebrafish TG (corolla: eGFP)	Immersion	1, 5, 20 μM	6 hours	To evaluate the effect of rhein on tail-cutting-induced immune cell migration in zebrafish larvae. Results showed that rhein dose-dependently inhibited the migration of immune cells toward the injured tail region.	Drug Des Devel Ther. 2017 Jun 6;11:1663-1671
BALB/c-nu mice	Oral cancer xenograft model	Intraperitoneal injection	10 and 50 mg/kg	3 times a week for 36 days	To evaluate the anticancer activity of Rhein in vivo. Results showed that Rhein significantly inhibited tumor growth without exhibiting obvious toxicity.	Int J Mol Sci. 2023 May 9;24(10):8507
C57BL/6J mice	Diet-induced obesity (DIO) model	Oral gavage	10 mg/kg/day	Once daily for 4 weeks	Rhein alleviates obesity, improves insulin sensitivity, and promotes white adipose tissue thermogenesis by inhibiting NLRP3 inflammasome activation in macrophages.	Commun Biol. 2024 Aug 16;7(1):1003
Nude mice	HCT116 xenograft model	Intraperitoneal injection	10, 50 mg/kg	Three times a week for 32 days	To evaluate the effect of Rhein on HCT116 xenograft tumor growth. Results showed that Rhein significantly inhibited tumor growth without obvious toxicity.	Cancers (Basel). 2021 Apr 30;13(9):2176
Db/db mice	Diabetic model	Oral	120 mg/kg	Once daily for 8 weeks	To investigate the effect of rhein on fasting blood glucose and glucose tolerance in db/db mice. Results showed that rhein significantly reduced fasting blood glucose levels and improved glucose tolerance.	Diabetes. 2013 Nov;62(11):3927-35
Sprague-Dawley rats	Retinal ischemia-reperfusion (RIR) injury model	Intravitreal injection	20 μM	Single injection, observed for 7 days	Rh-GFFYE significantly attenuated RIR injury, reduced retinal cell apoptosis, and improved retinal function	Adv Sci (Weinh). 2023 Oct;10(30):e2302909
Nude mice	LuCaP23.1 xenograft model	Oral	200 mg/kg	Twice daily until tumor volume reached ~2000 mm³	Significantly delayed and inhibited the growth of prostate cancer xenografts	Cell Rep Med. 2025 Jan 21;6(1):101890
Pigs	PRRSV infection model	Oral	25 mg/kg	Twice daily for three consecutive days	Evaluate the prophylactic and therapeutic effects of Tizoxanide on PRRSV in pigs, results showed 25 mg/kg dose significantly reduced viral load and lung lesions	Nat Commun. 2024 Jun 6;15(1):4813.
Landrace pigs	Landrace pigs model	Orally	25 mg/kg, 10 mg/kg, 5 mg/kg	Prophylactic (−1 dpi PO BID for 3 days) and therapeutic groups (3 dpi PO BID for 3 days)	NTZ inhibits PRRSV transmission.	Int J Mol Sci. 2017 Sep 20;18(9):2018.
Sprague-Dawley rats	Cerebral ischemic/reperfusion injury model	Oral	25, 50 or 100 mg/kg/day	Once daily for 3 days	To investigate the protective effects of Rhein on cerebral ischemic/reperfusion injury, the results showed that Rhein significantly improved neurological functional scores, reduced cerebral infarction area, and decreased oxidative stress and apoptosis markers.	Int J Mol Med. 2018 May;41(5):2802-2812
Sprague-Dawley rats	Severe acute pancreatitis (SAP) model	Gastric gavage	30 mg/kg	Once daily for 7 days	To investigate the protective effects of Rhein on the SAP rat model. Results showed that Rhein significantly alleviated pancreatic histopathological damage, reduced serum TNF-α and IL-6 levels, and inhibited the expression of JAK2/STAT3 signaling pathway-related proteins.	Front Pharmacol. 2022 Mar 17;13:778221
Kunming mice	Mastitis model	Mammary gland perfusion	40 μg/kg	Single administration, lasting 48 hours	Evaluate the therapeutic effect of Rhein on mastitis in mice, results showed that Rhein alleviated inflammation in mammary tissue, reduced the levels of TNF-α and IL-6, and decreased the number of S. xylosus.	Curr Res Food Sci. 2024 Mar 16;8:100718
C57BL/6J mice	LPS-induced ALI/ARDS model	Intraperitoneal injection	50 and 100 mg/kg	For 2 consecutive days	Rhein significantly attenuated tissue inflammation and promoted macrophage M2 polarization transition.	Inflamm Res. 2023 Jun;72(6):1237-1255
C57BL/6J mice	DSS-induced chronic colitis model	Oral gavage	50 mg/kg and 100 mg/kg	Daily administration until the end of the experiment	To evaluate the anti-inflammatory effects of Rhein on DSS-induced chronic colitis, results showed that Rhein significantly alleviated colitis symptoms, reduced inflammatory cytokine levels, and improved intestinal barrier function.	Theranostics. 2020 Aug 29;10(23):10665-10679
Hamsters	HFD-induced hyperlipidemia and hepatic steatosis model	Gavage	50, 100, 200 mg/kg/day	Once daily for 50 days	Ameliorated HFD-induced hyperlipidemia and hepatic steatosis	Acta Pharm Sin B. 2022 Mar;12(3):1322-1338
C57BL/6 mice	Transverse aortic constriction (TAC)-induced cardiac hypertrophy model	Oral gavage	50, 150, 200 mg/kg	Once daily for 28 days	To evaluate the inhibitory effect of Rhein on TAC-induced cardiac hypertrophy and fibrosis. Results showed that Rhein significantly improved cardiac function, reduced myocardial hypertrophy and fibrosis, and acted by inhibiting the STAT3 and p38 MAPK signaling pathways.	Front Pharmacol. 2022 Aug 26;13:940574
Syrian hamsters	SARS-CoV-2 infection model	Oral	500mg/kg/day BID or 750mg/kg/day TID	Twice or three times daily for 3 days	Evaluate the antiviral efficacy of Tizoxanide in vivo, showing no significant inhibition of viral replication	EBioMedicine. 2022 Aug;82:104148
BALB/c nude mice	PANC-1 and BxPC-3 xenograft models	Intraperitoneal injection	60 mg/kg rhein, 10 mg/kg erlotinib or the combination	Every two days for 28 days	Combined treatment with rhein and erlotinib significantly inhibited tumor growth, with significant reduction in tumor volume and weight compared to monotherapy	J Exp Clin Cancer Res. 2019 Jan 23;38(1):31

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CAS No.: 478-43-3

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CAS No.: 478-43-3

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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