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Article ; Online: Determination of doping higenamine in Chinese herbal medicines and their concentrated preparations by LC-MS/MS.

Lin, Yi-An / Hsu, Mei-Chich

Journal of pharmaceutical and biomedical analysis

2024 Volume 246, Page(s) 116188

Abstract: The World Anti-Doping Agency (WADA) has included higenamine in the β2 agonist (S3) category of the Prohibited List since 2017 due to its pharmacological effects on adrenergic receptors. Although higenamine contained in Chinese herbal medicines has been ... ...

Abstract	The World Anti-Doping Agency (WADA) has included higenamine in the β2 agonist (S3) category of the Prohibited List since 2017 due to its pharmacological effects on adrenergic receptors. Although higenamine contained in Chinese herbal medicines has been identified by previous studies, comprehensive investigation on the higenamine content of Chinese herbs and their concentrated preparations is still required. This study aimed to determine the levels of higenamine in Chinese medicinal materials and their concentrated preparations used in Chinese medicine prescriptions in Taiwan. The levels of higenamine in Chinese medicinal materials, including Cortex Phellodendri, Flos Caryophylli, Fructus Euodiae, Fructus Kochiae, Plumula Nelumbinis, Radix Aconiti Preparata, Radix Aconiti Lateralis Preparata, and Radix Asari, and their concentrated preparations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Our results showed that the amounts of higenamine were detected and quantified in studied Chinese medicinal materials and their concentrated preparations, except for Flos Caryophylli, Radix Aconiti Preparata, and Radix Aconiti Lateralis Preparata. Plumula Nelumbinis and Cortex Phellodendri have higher levels of higenamine when compared to other Chinese herbs tested in the present study. The highest level of higenamine was 2100 μg/g found in the Plumula Nelumbinis medicinal material. In contrast with Plumula Nelumbinis and Cortex Phellodendri, higenamine levels below 10 μg/g were found in other most of the studied Chinese medicinal materials and their concentrated preparations. This study confirmed that various Chinese herbs and their concentrated preparations contained higenamine, and it provided more coherent and comprehensive information for reducing the potential risk of higenamine misuse in sports.
Language	English
Publishing date	2024-05-01
Publishing country	England
Document type	Journal Article
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2024.116188
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Article ; Online: Coenzyme Q0 defeats NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects by inhibiting HIF-1α expression in human triple-negative breast cancer cells

Yang, Hsin-Ling / Lin, Ping-Yu / Vadivalagan, Chithravel / Lin, Yi'an / Lin, Kai-Yuan / Hseu, You-Cheng

Arch Toxicol 2023 Apr., v. 97, no. 4, p. 1047-1068

2023 , Page(s) 1047–1068

Abstract: Coenzyme Q₀ (CoQ₀) is a derivative quinone from Antrodia camphorata (AC) that exerts anticancer activities. This study examined the anticancer attributes of CoQ₀ (0–4 µM) on inhibited anti-EMT/metastasis and NLRP3 inflammasome, and altered Warburg ... ...

Abstract	Coenzyme Q₀ (CoQ₀) is a derivative quinone from Antrodia camphorata (AC) that exerts anticancer activities. This study examined the anticancer attributes of CoQ₀ (0–4 µM) on inhibited anti-EMT/metastasis and NLRP3 inflammasome, and altered Warburg effects via HIF-1α inhibition in triple-negative breast cancer (MDA-MB-231 and 468) cells. MTT assay, cell migration/invasion assays, Western blotting, immunofluorescence, metabolic reprogramming, and LC–ESI-MS were carried out to assess the therapy potential of CoQ₀. CoQ₀ inhibited HIF-1α expression and suppressed the NLRP3 inflammasome and ASC/caspase-1 expression, followed by downregulation of IL-1β and IL-18 expression in MDA-MB-231 and 468 cells. CoQ₀ ameliorated cancer stem-like markers by decreasing CD44 and increasing CD24 expression. Notably, CoQ₀ modulated EMT by upregulating the epithelial marker E-cadherin and downregulating the mesenchymal marker N-cadherin. CoQ₀ inhibited glucose uptake and lactate accumulation. CoQ₀ also inhibited HIF-1α downstream genes involved in glycolysis, such as HK-2, LDH-A, PDK-1, and PKM-2 enzymes. CoQ₀ decreased extracellular acidification rate (ECAR), glycolysis, glycolytic capacity, and glycolytic reserve in MDA-MB-231 and 468 cells under normoxic and hypoxic (CoCl₂) conditions. CoQ₀ inhibited the glycolytic intermediates lactate, FBP, and 2/3-PG, and PEP levels. CoQ₀ increased oxygen consumption rate (OCR), basal respiration, ATP production, maximal respiration, and spare capacity under normoxic and hypoxic (CoCl₂) conditions. CoQ₀ increased TCA cycle metabolites, such as citrate, isocitrate, and succinate. CoQ0 inhibited aerobic glycolysis and enhanced mitochondrial oxidative phosphorylation in TNBC cells. Under hypoxic conditions, CoQ₀ also mitigated HIF-1α, GLUT1, glycolytic-related (HK-2, LDH-A, and PFK-1), and metastasis-related (E-cadherin, N-cadherin, and MMP-9) protein or mRNA expression in MDA-MB-231 and/or 468 cells. Under LPS/ATP stimulation, CoQ₀ inhibited NLRP3 inflammasome/procaspase-1/IL-18 activation and NFκB/iNOS expression. CoQ₀ also hindered LPS/ATP-stimulated tumor migration and downregulated LPS/ATP-stimulated N-cadherin and MMP-2/-9 expression. The present study revealed that suppression of HIF-1α expression caused by CoQ₀ may contribute to inhibition of NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects of triple-negative breast cancers.
Keywords	Taiwanofungus camphoratus ; acidification ; breast neoplasms ; breasts ; cadherins ; cell movement ; citrates ; epithelium ; fluorescent antibody technique ; gene expression ; glucose ; glycolysis ; humans ; inflammasomes ; inflammation ; interleukin-18 ; lactic acid ; metabolites ; metastasis ; mitochondria ; oxidative phosphorylation ; oxygen consumption ; quinones ; succinic acid ; therapeutics ; toxicity testing ; tricarboxylic acid cycle
Language	English
Dates of publication	2023-04
Size	p. 1047-1068
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-023-03456-w
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Article ; Online: Coenzyme Q

Yang, Hsin-Ling / Lin, Ping-Yu / Vadivalagan, Chithravel / Lin, Yi-An / Lin, Kai-Yuan / Hseu, You-Cheng

Archives of toxicology

2023 Volume 97, Issue 4, Page(s) 1047–1068

Abstract: ... Coenzyme ... ...

Abstract	Coenzyme Q
MeSH term(s)	Humans ; Adenosine Triphosphate ; Cadherins/genetics ; Cell Line, Tumor ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Inflammasomes ; Inflammation ; Interleukin-18 ; Lactate Dehydrogenase 5 ; Lactates ; Lipopolysaccharides ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology ; Ubiquinone/pharmacology
Chemical Substances	Adenosine Triphosphate (8L70Q75FXE) ; Cadherins ; cobaltous chloride (EVS87XF13W) ; Hypoxia-Inducible Factor 1, alpha Subunit ; Inflammasomes ; Interleukin-18 ; Lactate Dehydrogenase 5 (EC 1.1.1.27.-) ; Lactates ; Lipopolysaccharides ; NLR Family, Pyrin Domain-Containing 3 Protein ; Ubiquinone (1339-63-5) ; NLRP3 protein, human ; HIF1A protein, human
Language	English
Publishing date	2023-02-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-023-03456-w
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Article ; Online: Lactiplantibacillus plantarum PS128 Alleviates Exaggerated Cortical Beta Oscillations and Motor Deficits in the 6-Hydroxydopamine Rat Model of Parkinson’s Disease

Ma, Yi-Fan / Lin, Yi'an / Huang, Chin-Lin / Hsu, Chih-Chieh / Wang, Sabrina / Yeh, Shih-Rung / Tsai, Ying-Chieh

Probiotics & Antimicro. Prot.. 2023 Apr., v. 15, no. 2 p.312-325

2023

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by midbrain dopaminergic neuronal loss and subsequent physical impairments. Levodopa manages symptoms best, while deep brain stimulation (DBS) is effective for advanced PD patients; ... ...

Abstract	Parkinson’s disease (PD) is a neurodegenerative disorder characterized by midbrain dopaminergic neuronal loss and subsequent physical impairments. Levodopa manages symptoms best, while deep brain stimulation (DBS) is effective for advanced PD patients; however, side effects occur with the diminishing therapeutic window. Recently, Lactiplantibacillus plantarum PS128 (PS128) was found to elevate dopamine levels in rodent brains, suggesting its potential to prevent PD. Here, the therapeutic efficacy of PS128 was examined in the 6-hydroxydopamine rat PD model. Suppression of the power spectral density of beta oscillations (beta PSD) in the primary motor cortex (M1) was recorded as the indicator of disease progression. We found that 6 weeks of daily PS128 supplementation suppressed M1 beta PSD as well as did levodopa and DBS. Long-term normalization of M1 beta PSD was found in PS128-fed rats, whereas levodopa and DBS showed only temporal effects. PS128 + levodopa and PS128 + DBS exhibited better therapeutic effects than did levodopa + DBS or either alone. Significantly improved motor functions in PS128-fed rats were correlated with normalization of M1 beta PSD. Brain tissue analyses further demonstrated the role of PS128 in dopaminergic neuroprotection and the enhanced availability of neurotransmitters. These findings suggest that psychobiotic PS128 might be used alongside conventional therapies to treat PD patients.
Keywords	L-dopa ; animal models ; disease progression ; dopamine ; motor cortex ; neurodegenerative diseases ; neurons ; neuroprotective effect ; neurotransmitters ; probiotics ; rats ; therapeutics
Language	English
Dates of publication	2023-04
Size	p. 312-325.
Publishing place	Springer US
Document type	Article ; Online
ZDB-ID	2487792-X
ISSN	1867-1314 ; 1867-1306
ISSN (online)	1867-1314
ISSN	1867-1306
DOI	10.1007/s12602-021-09828-x
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Article ; Online: American Ginseng Attenuates Eccentric Exercise-Induced Muscle Damage via the Modulation of Lipid Peroxidation and Inflammatory Adaptation in Males.

Lin, Ching-Hung / Lin, Yi-An / Chen, Shu-Li / Hsu, Mei-Chich / Hsu, Cheng-Chen

Nutrients

2021 Volume 14, Issue 1

Abstract: Exercise-induced muscle damage (EIMD) is characterized by a reduction in functional performance, disruption of muscle structure, production of reactive oxygen species, and inflammatory reactions. Ginseng, along with its major bioactive component ... ...

Abstract	Exercise-induced muscle damage (EIMD) is characterized by a reduction in functional performance, disruption of muscle structure, production of reactive oxygen species, and inflammatory reactions. Ginseng, along with its major bioactive component ginsenosides, has been widely employed in traditional Chinese medicine. The protective potential of American ginseng (AG) for eccentric EIMD remains unclear. Twelve physically active males (age: 22.4 ± 1.7 years; height: 175.1 ± 5.7 cm; weight: 70.8 ± 8.0 kg; peak oxygen consumption [V˙O2peak] 54.1 ± 4.3 mL/kg/min) were administrated by AG extract (1.6 g/day) or placebo (P) for 28 days and subsequently challenged by downhill (DH) running (-10% gradient and 60% V˙O2peak). The levels of circulating 8-iso-prostaglandin F 2α (PGF2α), creatine kinase (CK), interleukin (IL)-1β, IL-4, IL-10, and TNF-α, and the graphic pain rating scale (GPRS) were measured before and after supplementation and DH running. The results showed that the increases in plasma CK activity induced by DH running were eliminated by AG supplementation at 48 and 72 h after DH running. The level of plasma 8-iso-PGF2α was attenuated by AG supplementation immediately (
MeSH term(s)	Cytokines/genetics ; Cytokines/metabolism ; Double-Blind Method ; Exercise/adverse effects ; Gene Expression Regulation/drug effects ; Humans ; Inflammation/drug therapy ; Lipid Peroxidation/drug effects ; Male ; Muscular Diseases/drug therapy ; Muscular Diseases/etiology ; Panax/chemistry ; Phytotherapy ; Plant Extracts/chemistry ; Plant Extracts/therapeutic use ; Young Adult
Chemical Substances	Cytokines ; Plant Extracts
Language	English
Publishing date	2021-12-25
Publishing country	Switzerland
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14010078
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy.

Lin, Yi-An / Li, Yan-Rong / Chang, Yi-Ching / Hsu, Mei-Chich / Chen, Szu-Tah

Scientific reports

2021 Volume 11, Issue 1, Page(s) 10790

Abstract: The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium ... ...

Abstract	The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Line ; Chromones/pharmacology ; Flavonoids/pharmacology ; Gene Expression Regulation/drug effects ; Hypertrophy ; Insulin-Like Growth Factor I/genetics ; Insulin-Like Growth Factor I/metabolism ; Mice ; Morpholines/pharmacology ; Myoblasts/cytology ; Myoblasts/drug effects ; Myoblasts/metabolism ; Myoblasts/pathology ; Myosin Heavy Chains/genetics ; Myosin Heavy Chains/metabolism ; Podophyllotoxin/analogs & derivatives ; Podophyllotoxin/pharmacology ; Signal Transduction/drug effects ; Sirolimus/pharmacology
Chemical Substances	Chromones ; Flavonoids ; Morpholines ; insulin-like growth factor-1, mouse ; picropodophyllin (0F35AOI227) ; 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (31M2U1DVID) ; Insulin-Like Growth Factor I (67763-96-6) ; Myosin Heavy Chains (EC 3.6.4.1) ; Podophyllotoxin (L36H50F353) ; icariin (VNM47R2QSQ) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2021-05-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-89039-0
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Article: Where Are the Proto‐South China Sea Slabs? SE Asian Plate Tectonics and Mantle Flow History From Global Mantle Convection Modeling

Lin, Yi‐An / Colli, Lorenzo / Wu, Jonny / Schuberth, Bernhard S. A.

Journal of geophysical research. 2020 Dec., v. 125, no. 12

2020

Abstract: The plate tectonic history of the hypothesized “proto‐South China Sea” (PSCS) ocean basin and surrounding SE Asia since Cenozoic times is controversial. We implement four diverse proto‐South China Sea plate reconstructions into global geodynamic models ... ...

Abstract	The plate tectonic history of the hypothesized “proto‐South China Sea” (PSCS) ocean basin and surrounding SE Asia since Cenozoic times is controversial. We implement four diverse proto‐South China Sea plate reconstructions into global geodynamic models to constrain PSCS plate tectonics and possible slab locations. Our plate reconstructions consider the following: southward versus double‐sided PSCS subduction models; earlier (Eocene) or later (late Oligocene) initiation of Borneo counterclockwise rotations; and larger or smaller reconstructed Philippine Sea plate sizes. We compare our modeling results against tomographic images by accounting for mineralogical effects and the finite resolution of seismic tomography. All geodynamic models reproduce the tomographically imaged Sunda slabs beneath Peninsular Malaysia, Sumatra, and Java. Southward PSCS subduction produces slabs beneath present Palawan, northern Borneo, and offshore Palawan. Double‐sided PSCS subduction combined with earlier Borneo rotations uniquely reproduces subhorizontal slabs under the southern South China Sea (SCS) at ~400 to 700 km depths; these models best fit seismic tomography. A smaller Philippine Sea (PS) plate with a ~1,000‐km‐long restored Ryukyu slab was superior to a very large PS plate. Considered together, our four end‐member plate reconstructions predict that the PSCS slabs are now at <900 km depths under present‐day Borneo, the SCS, the Sulu and Celebes seas, and the southern Philippines. Regardless of plate reconstruction, we predict (1) mid‐Cenozoic passive return‐flow upwellings under Indochina; and (2) late Cenozoic downwellings under the SCS that do not support a deep‐origin “Hainan plume.” Modeled Sundaland dynamic topography strongly depends on the imposed plate reconstructions, varying by almost 1 km.
Keywords	Borneo ; Eocene epoch ; Oligocene epoch ; Philippines ; basins ; convection ; geophysics ; research ; subduction ; tectonics ; tomography ; topography ; China ; Indochina ; Indonesia ; Malaysia ; Philippine Sea ; South China Sea
Language	English
Dates of publication	2020-12
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ISSN	2169-9313
DOI	10.1029/2020JB019758
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Article: American Ginseng Attenuates Eccentric Exercise-Induced Muscle Damage via the Modulation of Lipid Peroxidation and Inflammatory Adaptation in Males

Lin, Ching-Hung / Lin, Yi-An / Chen, Shu-Li / Hsu, Mei-Chich / Hsu, Cheng-Chen

Nutrients. 2021 Dec. 25, v. 14, no. 1

2021

Abstract	Exercise-induced muscle damage (EIMD) is characterized by a reduction in functional performance, disruption of muscle structure, production of reactive oxygen species, and inflammatory reactions. Ginseng, along with its major bioactive component ginsenosides, has been widely employed in traditional Chinese medicine. The protective potential of American ginseng (AG) for eccentric EIMD remains unclear. Twelve physically active males (age: 22.4 ± 1.7 years; height: 175.1 ± 5.7 cm; weight: 70.8 ± 8.0 kg; peak oxygen consumption [V˙O2peak] 54.1 ± 4.3 mL/kg/min) were administrated by AG extract (1.6 g/day) or placebo (P) for 28 days and subsequently challenged by downhill (DH) running (−10% gradient and 60% V˙O2peak). The levels of circulating 8-iso-prostaglandin F 2α (PGF2α), creatine kinase (CK), interleukin (IL)-1β, IL-4, IL-10, and TNF-α, and the graphic pain rating scale (GPRS) were measured before and after supplementation and DH running. The results showed that the increases in plasma CK activity induced by DH running were eliminated by AG supplementation at 48 and 72 h after DH running. The level of plasma 8-iso-PGF2α was attenuated by AG supplementation immediately (p = 0.01 and r = 0.53), 2 h (p = 0.01 and r = 0.53) and 24 h (p = 0.028 and r = 0.45) after DH running compared with that by P supplementation. Moreover, our results showed an attenuation in the plasma IL-4 levels between AG and P supplementation before (p = 0.011 and r = 0.52) and 72 h (p = 0.028 and r = 0.45) following DH running. Our findings suggest that short-term supplementation with AG alleviates eccentric EIMD by decreasing lipid peroxidation and promoting inflammatory adaptation.
Keywords	Oriental traditional medicine ; Panax quinquefolius ; bioactive compounds ; creatine kinase ; exercise ; ginsenosides ; interleukin-10 ; interleukin-4 ; lipid peroxidation ; muscles ; oxygen consumption ; pain ; placebos ; reactive oxygen species
Language	English
Dates of publication	2021-1225
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14010078
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: In vitro and in vivo anti-tumor activity of Antrodia salmonea against twist-overexpressing HNSCC cells: Induction of ROS-mediated autophagic and apoptotic cell death.

Yang, Hsin-Ling / Lin, Yi-An / Pandey, Sudhir / Liao, Jiunn-Wang / Way, Tzong-Der / Yeh, Yu-Lyu / Chen, Siang-Jyun / Hseu, You-Cheng

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2022 Volume 172, Page(s) 113564

Abstract: Head and neck squamous cell carcinoma (HNSCC) is a relatively common malignancy, characterized by lethal morbidity. Herein, we attempted to investigate the autophagy/apoptosis activities of the submerged fermented broths of Antrodia salmonea (AS) in ... ...

Abstract	Head and neck squamous cell carcinoma (HNSCC) is a relatively common malignancy, characterized by lethal morbidity. Herein, we attempted to investigate the autophagy/apoptosis activities of the submerged fermented broths of Antrodia salmonea (AS) in HNSCC Twist-overexpressing (OECM-1 and FaDu-Twist) cells. AS (0-150 μg/mL) effectively reduced cell viability, colony formation, and downregulated Twist expression in OECM-1 and FaDu-Twist cells compared to FaDu cells. AS- induced apoptosis was mainly associated with activation of caspase-3, PARP cleavage, increased expression of VDAC-1 and disproportionation of Bax/Bcl-2. Annexin V/PI staining suggested late apoptosis induction by AS treatment. AS exhibits enhanced autophagy process mediated via LC3-I/II accumulation, increased acidic vesicular organelles (AVOs) formation and p62/SQSTM1 expression feeding into the apoptotic program. However, pre-treatment with autophagy blockers 3-MA and CQ significantly diminished AS-induced cell death. Additionally, suppression of AS-induced ROS release by treatment with antioxidant N-acetylcysteine (NAC) resulted in reduction of apoptotic and autophagic cell death. In vivo studies strengthened the above observations and showed that AS effectively reduced the tumor volume and tumor weight in OECM-1-xenografted nude mice. This study discovered that Antrodia salmonea exhibits a novel anti-cancer mechanism which could be harnessed as a new potent drug for HNSCC treatment.
MeSH term(s)	Animals ; Mice ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Reactive Oxygen Species/metabolism ; Mice, Nude ; Apoptosis ; Autophagy ; Cell Line, Tumor ; Head and Neck Neoplasms/drug therapy
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2022-12-20
Publishing country	England
Document type	Journal Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2022.113564
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Article ; Online: Urinary excretion patterns and potential risks of beta-blocker ophthalmic drops in sports.

Lin, Yi-An / Chiang, Wei-Yu / Chang, William Chih-Wei / Kuo, Ming-Tse / Chen, Alexander / Hsu, Mei-Chich

Drug testing and analysis

2022 Volume 15, Issue 1, Page(s) 75–83

Abstract: Beta-blockers have been prohibited by the World Anti-Doping Agency (WADA) in certain sports, but insufficient research data make it difficult to distinguish between therapeutic uses or misuses. This study aimed at investigating the urinary excretion ... ...

Abstract	Beta-blockers have been prohibited by the World Anti-Doping Agency (WADA) in certain sports, but insufficient research data make it difficult to distinguish between therapeutic uses or misuses. This study aimed at investigating the urinary excretion pattern following beta-blocker ophthalmic drops and the potential risk of constituting an adverse analytical finding (AAF) in sports. Prescribed timolol and carteolol ophthalmic drops were used in healthy participants and glaucoma patients. The urine samples were then collected to investigate the urinary excretion pattern following acute and chronic administration of the above beta-blocker ophthalmic drops. The liquid chromatograph-tandem mass spectrometry method was applied for measuring urinary beta-blockers. Our results demonstrated that the levels of both urinary timolol and carteolol exceeded the minimum reporting levels (MRL) following acute and chronic administration. The highest levels of urinary timolol and carteolol observed in the present study were 255.7 and 923.8 ng/ml, respectively. Regarding the acute administration of timolol ophthalmic drop, 26.19 (11/42) of urine samples were detected with timolol higher than the MRL in timed and random sampling. In contrast, the acute administration of carteolol ophthalmic drops made the carteolol levels higher than the MRL among most urine samples. On the other hand, 36.36% (4/11) of urine samples were detected with beta-blockers higher than the MRL during the chronic administration of timolol and carteolol ophthalmic drops. In the context of receiving ophthalmic beta-blocker medications, the present study has highlighted the potential risk of constituting an AAF in specific sports and suggests strengthening athletes' awareness of therapeutic use exemptions.
MeSH term(s)	Humans ; Timolol/adverse effects ; Carteolol/adverse effects ; Adrenergic beta-Antagonists ; Ophthalmic Solutions/adverse effects ; Sports
Chemical Substances	Timolol (817W3C6175) ; Carteolol (8NF31401XG) ; Adrenergic beta-Antagonists ; Ophthalmic Solutions
Language	English
Publishing date	2022-11-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2462336-2
ISSN	1942-7611 ; 1942-7603
ISSN (online)	1942-7611
ISSN	1942-7603
DOI	10.1002/dta.3368
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