Oroxylin A(OA),a natural compound extracted from Scutellaria baicalensis,demonstrates preventive potential against ultraviolet B(UVB)-induced non-melanoma skin cancer(NMSC),the most prevalent cancer worldwide with inc...Oroxylin A(OA),a natural compound extracted from Scutellaria baicalensis,demonstrates preventive potential against ultraviolet B(UVB)-induced non-melanoma skin cancer(NMSC),the most prevalent cancer worldwide with increasing incidence.Utilizing SKH-1 hairless mice exposed to UVB,this study showed that OA delayed NMSC onset and alleviated acute skin damage.Mechanistic investigations revealed its dual action:inhibiting inflammation and enhancing nucleotide excision repair(NER)by stabilizing XPA,a crucial deoxyribonucleic acid(DNA)repair protein.This stabilization occurred through OA's interaction with glucose-regulated protein 94(GRP94),which disrupted murine double minute 2(MDM2)-mediated XPA ubiquitination and proteasomal degradation.By maintaining XPA levels,OA expedited photoproduct clearance and diminished genomic instability,ultimately impeding NMSC development.These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.展开更多
Oroxylin A(OA)is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis.Currently,OA is obtainable through chemical synthesis and exhibits polypharmacological properties,inc...Oroxylin A(OA)is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis.Currently,OA is obtainable through chemical synthesis and exhibits polypharmacological properties,including anti-cancer,anti-inflammatory,anti-microbial,and multi-organ protective effects.The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma(HCC)treatment.Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal(GI)disorders,including HCC,hepatic fibrosis,fatty liver disease,hepatitis,liver injury,colitis,and colorectal cancer(CRC).OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways,including those associated with apoptosis,oxidative stress,inflammation,glucolipid metabolism,and fibrosis activation.The oral pharmacokinetics of OA is characterized by phase II metabolism,hydrolysis,and enterohepatic recycling.This review provides a comprehensive overview of the critical stages involved in the development of OA tablets,presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases.It encompasses the synthesis of active pharmaceutical ingredients,pharmacokinetics,pharmacological efficacy,toxicology,drug delivery,and recent advancements in clinical trials.Importantly,this review examines the potential mechanisms by which OA may influence the gut-liver axis,hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.展开更多
Xiao-xu-ming decoction(XXMD)is a traditional Chinese medicine that has been widely used to treat theoplegia and its sequelae.This paper reports the development of three separate assays based on reversed phase high-per...Xiao-xu-ming decoction(XXMD)is a traditional Chinese medicine that has been widely used to treat theoplegia and its sequelae.This paper reports the development of three separate assays based on reversed phase high-performance liquid chromatography–mass spectrometry(HPLC–MS)and HPLC–MS/MS for the determination of seven active constituents of XXMD viz oroxylin A-7-O-glucuronide,wogonoside,liquiritigenin,cimifugin,5-O-methylvisammiol,glycyrrhizic acid and glycyrrhetinic acid in rat plasma.All calibration curves were linear(r >0.99)with lower limits of quantitation(LLOQs)<12.4 ng/mL.Intra-and inter-day precisions(as relative standard deviation)were all <10.7% with recoveries in the range of 88.7–113%.In addition,the seven analytes were shown to be stable in rat plasma samples under relevant storage conditions.The validated methods were successfully applied to a pharmacokinetic study in rat after oral administration of XXMD.展开更多
基金supported by the National Natural Science Foundation of China(No.81974425)the Natural Science Foundation of Jiangsu Province(Nos.BK20211578 and BK20210419)+1 种基金the China Postdoctoral Science Foundation Grant(No.2021M693513)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX22-0794)。
文摘Oroxylin A(OA),a natural compound extracted from Scutellaria baicalensis,demonstrates preventive potential against ultraviolet B(UVB)-induced non-melanoma skin cancer(NMSC),the most prevalent cancer worldwide with increasing incidence.Utilizing SKH-1 hairless mice exposed to UVB,this study showed that OA delayed NMSC onset and alleviated acute skin damage.Mechanistic investigations revealed its dual action:inhibiting inflammation and enhancing nucleotide excision repair(NER)by stabilizing XPA,a crucial deoxyribonucleic acid(DNA)repair protein.This stabilization occurred through OA's interaction with glucose-regulated protein 94(GRP94),which disrupted murine double minute 2(MDM2)-mediated XPA ubiquitination and proteasomal degradation.By maintaining XPA levels,OA expedited photoproduct clearance and diminished genomic instability,ultimately impeding NMSC development.These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
基金supported by the National Natural Science Foundation of China(No.82174027)the Social Development Project of Jiangsu Provincial Key Research and Development Program(No.BE2021782)Qinglan Project of Jiangsu Province.
文摘Oroxylin A(OA)is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis.Currently,OA is obtainable through chemical synthesis and exhibits polypharmacological properties,including anti-cancer,anti-inflammatory,anti-microbial,and multi-organ protective effects.The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma(HCC)treatment.Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal(GI)disorders,including HCC,hepatic fibrosis,fatty liver disease,hepatitis,liver injury,colitis,and colorectal cancer(CRC).OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways,including those associated with apoptosis,oxidative stress,inflammation,glucolipid metabolism,and fibrosis activation.The oral pharmacokinetics of OA is characterized by phase II metabolism,hydrolysis,and enterohepatic recycling.This review provides a comprehensive overview of the critical stages involved in the development of OA tablets,presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases.It encompasses the synthesis of active pharmaceutical ingredients,pharmacokinetics,pharmacological efficacy,toxicology,drug delivery,and recent advancements in clinical trials.Importantly,this review examines the potential mechanisms by which OA may influence the gut-liver axis,hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.
基金the National Natural Science Foundation of China(No.30630073)the Innovation Method Fund from Ministry of Science and Technology of China(2009IM031600)for financial support.
文摘Xiao-xu-ming decoction(XXMD)is a traditional Chinese medicine that has been widely used to treat theoplegia and its sequelae.This paper reports the development of three separate assays based on reversed phase high-performance liquid chromatography–mass spectrometry(HPLC–MS)and HPLC–MS/MS for the determination of seven active constituents of XXMD viz oroxylin A-7-O-glucuronide,wogonoside,liquiritigenin,cimifugin,5-O-methylvisammiol,glycyrrhizic acid and glycyrrhetinic acid in rat plasma.All calibration curves were linear(r >0.99)with lower limits of quantitation(LLOQs)<12.4 ng/mL.Intra-and inter-day precisions(as relative standard deviation)were all <10.7% with recoveries in the range of 88.7–113%.In addition,the seven analytes were shown to be stable in rat plasma samples under relevant storage conditions.The validated methods were successfully applied to a pharmacokinetic study in rat after oral administration of XXMD.
