ABSTRACT
Objective: To study the effects of acupuncture combined with the formula of Yi Qi Yang Yin and blood activating (A-YBF) on blood glucose levels and renal function in patients with early diabetic nephropathy. Methods: 96 patients with early diabetic nephropathy treated in our hospital from April 2021 to April 2022 were included in the study and divided into the control group (conventional medical treatment) and the study group (A-YBF), with 48 cases in each group. The efficacy and adverse effects were recorded by comparing the Chinese medicine symptom points, blood glucose level, renal function, and inflammatory factor level between the two groups before and after the treatment. Results: The clinical efficacy of the study group was significantly higher than that of the control group (P < .05). Before treatment, no difference was found between the primary and secondary symptom scores of the two groups (P > .05); after treatment, the primary and secondary symptom scores of the study group were lower than those of the control group (P < .05). Before treatment, there was no difference in fasting blood glucose (FPG) and 2h postprandial glucose (2hPG) levels; 24h urine protein quantification, cystatin C (Cys-C), urinary albumin excretion rate (UAER), and estimated glomerular filtration rate (eGFR) levels; and growth differentiation factor-15 (GDF-15), interleukin-1ß (IL-1ß), interleukin-17 (IL-17), and serum amyloid A (SAA) levels between the two groups (P > .05). After treatment, FPG and 2hPG levels; 24h urine protein quantification, Cys-C and UAER levels; and GDF-15, IL-1ß, IL-17, and SAA levels were lower in the study group than in the control group, while eGFR levels were higher than those in the control group (P < .05). Conclusion: A-YBF can effectively reduce blood glucose levels and improve renal function in patients with early diabetic nephropathy and can be promoted in clinical application.
ABSTRACT
Magnetic resonance imaging (MRI) is an important tool in the diagnosis of many cancers. However, clinical gadolinium (Gd)-based MRI contrast agents have limitations, such as large doses and potential side effects. To address these issues, we developed a hydrogen-bonded organic framework-based MRI contrast agent (PFC-73-Mn). Due to the hydrogen-bonded interaction of water molecules and the restricted rotation of manganese ions, PFC-73-Mn exhibits high longitudinal relaxation r1 (5.03 mM-1 s-1) under a 3.0 T clinical MRI scanner. A smaller intravenous dose (8 µmol of Mn/kg) of PFC-73-Mn can provide strong contrast and accurate diagnosis in multiple kinds of cancers, including breast tumor and ultrasmall orthotopic glioma. PFC-73-Mn represents a prospective new approach in tumor imaging, especially in early-stage cancer.
Subject(s)
Glioma , Manganese , Humans , Contrast Media , Gadolinium , Magnetic Resonance Imaging/methodsABSTRACT
Objective: This study aimed to investigate the efficacy of holographic meridian scraping therapy on patients with knee osteoarthritis (KOA) and its impact on serum IL-1ß and TNF-α levels. Methods: A prospective study was conducted, enrolling seventy KOA patients admitted to the Hebei Provincial Hospital of Traditional Chinese Medicine between August 2021 and April 2022. The patients were divided into two groups using the random number table method: control group (n = 35) and treatment group (n = 35). The control group received oral celecoxib capsules (100 mg, twice daily), while the treatment group received an additional daily holographic meridian scraping session (20 minutes/day). Throughout the two-week study, the researchers continuously monitored the visual analogue scale (VAS) score, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and the changes in serum IL-1ß and TNF-α expression. Results: The treatment group demonstrated significantly better overall efficiency and efficacy compared to the control group (P < .05). Both groups exhibited decreased VAS and WOMAC scores after treatment in comparison to pre-treatment levels (P < .05), with the treatment group showing lower scores than the control group after treatment (P < .05). Furthermore, serum TNF-α and IL-1ß levels in both groups decreased after treatment compared to pre-treatment levels within the same group (P < .05). The treatment group had significantly lower serum TNF-α and IL-1ß levels than the control group after treatment (P < .05). Conclusions: Combining holographic meridian scraping therapy with celecoxib effectively treats KOA and significantly improves patient conditions, along with reductions in serum TNF-α and IL-1ß levels.
Subject(s)
Meridians , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/drug therapy , Celecoxib/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic use , Prospective Studies , Treatment OutcomeABSTRACT
Six new non-classical cardenolides (1-6), and seventeen known ones (7-23) were isolated from Calotropis gigantea. All cardenolides showed inhibitory effect on hypoxia inducible factor-1 (HIF-1) transcriptional activity with IC50 of 8.85 nM-16.69 µM except 5 and 7. The novel 19-dihydrocalotoxin (1) exhibited a comparable HIF-1 inhibitory activity (IC50 of 139.57 nM) to digoxin (IC50 of 145.77 nM), a well-studied HIF-1 inhibitor, and 11, 12, 14, 16 and 19 presented 1.4-15.4 folds stronger HIF-1 inhibition than digoxin. 1 and 11 showed a dose-dependent inhibition on HIF-1α protein, which led to their HIF-1 suppressing effects. Compared with LO2 and H9c2 normal cell lines, both 1 and 11 showed selective cytotoxicity against various cancer cell lines including HCT116, HeLa, HepG2, A549, MCF-7, A2780 and MDA-MB-231. Moreover, a comprehensive structure-activity relationship was concluded for these non-classical cardenolides as HIF-1 inhibitors, which may shed some light on the rational design and development of cardenolide-based anticancer drugs.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Calotropis/chemistry , Cardenolides/pharmacology , Hypoxia-Inducible Factor 1/antagonists & inhibitors , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cardenolides/chemistry , Cardenolides/isolation & purification , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Conformation , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Structure-Activity RelationshipABSTRACT
Magnolol, a natural bioactive neolignan, was found in the bark of a traditional Chinese medicine Magnoliae officinalis ("Hou Po" in Chinese). In this study, thrity-two magnolol-based Mannich base derivatives 3a-p and 4a-p were synthesized, and evaluated for their anti-proliferative activities against a panel of human tumor cell lines (T47D, MCF-7, Hela and A549). Among all derivatives, compound 3p displayed the most potent antiproliferative activity against T47D, MCF-7 and Hela cell lines with IC50 values of 0.91, 3.32 and 1.71 µM, respectively. Compared with the parental magnolol and the positive drug cisplatin, 3p exhibited up to 76.1-fold and 10.3-fold enhancement of cytotoxic effect on T47D cancer cells, respectively. Mechanism study revealed that the most potent derivative 3p suppressed cancer cells via inducing autophagy. Moreover, 3p also possessed suppressive effects on migration of T47D and Hela cancer cells. In addition, some interesting structure-activity relationships (SARs) were also summarized.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Autophagy/drug effects , Biphenyl Compounds/chemical synthesis , Biphenyl Compounds/pharmacology , Lignans/chemical synthesis , Lignans/pharmacology , Antineoplastic Agents/chemistry , Biphenyl Compounds/chemistry , Cell Line, Tumor , Chemistry Techniques, Synthetic , Humans , Lignans/chemistry , Mannich Bases/chemistry , Structure-Activity RelationshipABSTRACT
The interaction behavior between food bio-macromolecules is the key point to develop the novel functional food ingredients. Effects of high pressure (HP) or microwave treatment (MW) on the physicochemical properties and microstructures of soy protein hydrolysates (SH)/ß-glucan/ferulic acid complexes (S-G-F) were investigated. The results showed that both HP and MW treatment significantly reduced the S-G-F complex particle size and fluorescence intensity along with the improved thermal stability and antioxidant activity but did not affect the zeta potential and the crystal structure. HP treatment changed the conformation of SH by increasing the ß-sheet content and decreasing the unordered structure, while MW treatment induce the increase in random coils content and the decreased in the α-helix content of SH. Accordingly, compared with MW treatment, HP treatment could result in the formation of a more compact structure with the uniform distribution through the stronger hydrogen bonding and hydrophobic interaction between components. This work revealed the interaction behaviors of food multi-component self-assembled nanoscale aggregation under high-technology in the food processing, which could provide a new direction for the development of antioxidant food ingredients by effectively utilizing the interaction between food components.
Subject(s)
Coumaric Acids/chemistry , Food Handling/methods , Food Technology/methods , Microwaves , Protein Hydrolysates/chemistry , Soybean Proteins/chemistry , beta-Glucans/chemistry , Antioxidants , Hydrophobic and Hydrophilic Interactions , Particle Size , Pressure , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , X-Ray DiffractionABSTRACT
Aim: To design novel emulsifiers with the ability to improve the storage and digestion stability of curcumin emulsions, besides to investigate the influence of phenolic acids types on the emulsify ability of soy protein-pectin-phenolic acids complexes obtained by ultrasonication. Methods: The ternary complexes were characterised by particle size, morphology, zeta potential, X-ray diffraction, Fourier transform infra-red and fluorescence spectroscopy. Additionally, changes in droplet size, charge, and microstructure were monitored as quantitative stability index of curcumin emulsions. Results: Phenolic acid types significantly affected the formation of ternary complexes. Soy protein-pectin-ferulic acid complex (S-P-F) stabilised curcumin emulsion had the best emulsifying property, followed by soy protein-pectin- ellagic acid (S-P-E), and soy protein-pectin-tannic acid complexes (S-P-T). Moreover, S-P-F emulsion was found to retain efficiently cucumin within 30 days storage (77.35%) and simulated gastrointestinal tract (64.09%). Conclusion: Protein-polysaccharide-phenolic acids emulsions are effective oral delivery systems for hydrophobic bioactives.
Subject(s)
Antineoplastic Agents/administration & dosage , Curcumin/administration & dosage , Emulsions/chemistry , Hydroxybenzoates/chemistry , Pectins/chemistry , Soybean Proteins/chemistry , Antineoplastic Agents/chemistry , Curcumin/chemistry , Digestion , Drug Carriers/chemistry , Drug Stability , Emulsifying Agents/chemistry , HumansABSTRACT
OBJECTIVES: To evaluate the relationship between cancer history and cost-related medication nonadherence (CRN) as well as cost-coping strategies, by health insurance coverage. METHODS: We used the 2013 to 2016 National Health Interview Survey to identify adults aged 18 to 64 years with (n = 3599) and without (n = 56 909) a cancer history. Cost-related changes in medication use included (1) CRN, measured as skipping, taking less, or delaying medication because of cost, and (2) cost-coping strategies, measured as requesting lower cost medication or using alternative therapies to save money. Separate multivariable logistic regressions were used to calculate the adjusted odds ratios (AORs) of CRN and cost-coping strategies associated with cancer history, stratified by insurance. RESULTS: Cancer survivors were more likely than adults without a cancer history to report CRN (AOR 1.26; 95% confidence interval [CI] 1.10-1.43) and cost-coping strategies (AOR 1.10; 95% CI 0.99-1.19). Among the privately insured, the difference in CRN by cancer history was the greatest among those enrolled in high-deductible health plans (HDHPs) without health savings accounts (HSAs) (AOR 1.78; 95% CI 1.30-2.44). Among adults with HDHP and HSA, cancer survivors were less likely to report cost-coping strategies (AOR 0.62; 95% CI 0.42-0.90). Regardless of cancer history, CRN and cost-coping strategies were the highest for those uninsured, enrolled in HDHP without HSA, and without prescription drug coverage under their health plan (all P<.001). CONCLUSIONS: Cancer survivors are prone to CRN and more likely to use cost-coping strategies. Expanding options for health insurance coverage, use of HSAs for those with HDHP, and enhanced prescription drug coverage may effectively address CRN.
Subject(s)
Antineoplastic Agents/economics , Antineoplastic Agents/therapeutic use , Cancer Survivors/psychology , Health Expenditures , Insurance Coverage/economics , Insurance, Health/economics , Medication Adherence , Neoplasms/drug therapy , Neoplasms/economics , Adolescent , Adult , Cost Savings , Deductibles and Coinsurance/economics , Drug Substitution/economics , Drugs, Generic/economics , Drugs, Generic/therapeutic use , Female , Health Care Surveys , Health Knowledge, Attitudes, Practice , Humans , Male , Medical Savings Accounts , Middle Aged , Neoplasms/epidemiology , Neoplasms/psychology , Time Factors , United States/epidemiology , Young AdultABSTRACT
Parkinson's Disease (PD) is the second most common neurodegenerative disease with the clinical characteristics of gait deficits. The classical symptomatic treatment for PD is Levodopa (L-DOPA) which brings a plethora of side effects and dosage problems in a prolonged drug regimen. Baicalein is a flavonoid extracted from Scutellaria baicalensis Georgi with the properties of neuroprotection. In this study, we investigated the ameliorative effect of baicalein with low dose L-DOPA (25â¯mg/kg) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinsonism. The gait variability was assessed by a computer-assisted gait analysis system Catwalk. The results showed that MPTP challenged mice had significant gait deficits on dynamic paw function and posture stability. L-DOPA reversed the MPTP induced gait deficits and the effect was positively dose-dependent. The combined treatment of baicalein and under threshold dose of L-DOPA significantly improved gait functions, compared with exclusive low dose L-DOPA treatment, and the effect was comparable with high dose L-DOPA treatment. The histological assessment demonstrated that the Tyrosine hydroxylase expression increased in all the baicalein stratified groups, which suggest baicalein might have the neuroprotective effect to retain the dopaminergic neurons or enhance the dopaminergic neuron regeneration after MPTP injection. This neuroprotection probably depended on altering the inflammatory response and resisting the apoptosis through the underlying mechanism investigation. Our study provides experimental evidence that the combination of L-DOPA and baicalein might be a potential treatment for Parkinson's disease. The synergistic interaction of baicalein and L-dopa treatment might reduce the side-effect of the normal to high dose L-DOPA used today.
Subject(s)
Antiparkinson Agents/pharmacology , Dopaminergic Neurons/drug effects , Flavanones/pharmacology , Levodopa/pharmacology , Parkinsonian Disorders/physiopathology , Animals , Disease Models, Animal , Gait/drug effects , Male , Mice , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Scutellaria baicalensisABSTRACT
Nine new monomacrolide sesquiterpene pyridine alkaloids, macroregelines A-I (1-9), were isolated from the stems of Tripterygium regelii, along with a known alkaloid, tripfordine B. The structures of all the isolated compounds were characterized by extensive one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopic analyses, as well as high-resolution electrospray-ionization mass spectrometry (HRESIMS) data. Compounds 4, 5, 6, and 8 showed antiproliferative effect on human rheumatoid arthritis synovial cell line MH7A at concentration of 20 µM, reducing their viability by 7.5, 18.0, 9.0, and 18.2 %, respectively.
Subject(s)
Alkaloids/chemistry , Macrolides/chemistry , Pyridines/chemistry , Sesquiterpenes/therapeutic use , Tripterygium/chemistry , Drugs, Chinese Herbal/chemistry , Humans , Sesquiterpenes/pharmacologyABSTRACT
Zuotai, also named as "gTso thal", a known Tibetan medicinal mixture containing insoluble cubic crystal mercuric sulfide (ß-HgS), has been used to treat diseases with long history. The mercury release ratio from Zuotai in gastrointestinal environment is one determinant factor for its bioavailability and biological effect. However, the information is still scarce now. Therefore, the study was designed to investigate the effect of sulfhydryl biomolecules [L-cysteine (Cys) and glutathione (GSH)] and pH on mercury dissociation from Zuotai, ß-HgS, and hexagonal crystal mercuric sulfide (α-HgS) in artificial gastrointestinal juices or pure water with a 1:100 solid-liquid ratio. And, the digestion and peristalsis of gastrointestinal tract were simulated in vitro. The results showed the following trend for the mercury release ratio of Zuotai, artificial gastric juice > artificial intestinal juice > pure water, whereas the trend for ß-HgS and α-HgS was as follows, artificial intestinal fluid > artificial gastric fluid > pure water. The mercury release ratios of Zuotai, ß-HgS, and α-HgS significantly increased in artificial intestinal juice containing L-Cys or GSH compared to those without sulfhydryl biomolecules in the juice. However, in contrast to the results observed for ß-HgS and α-HgS, the mercury release ratio of Zuotai was reduced remarkably in pure water and artificial gastric juice with Cys or GSH. And, we found that strong acidic or strong alkaline environments promoted the dissociation of mercury from Zuotai, ß-HgS, and α-HgS. Taken together, current findings may contribute to other studies regarding clinical safety and bioavailability of the traditional drug Zuotai containing ß-HgS.
Subject(s)
Cysteine/pharmacology , Drug Liberation/drug effects , Glutathione/pharmacology , Mercury Compounds/pharmacokinetics , Mercury/pharmacokinetics , Biological Availability , Gastric Juice/chemistry , Gastric Juice/metabolism , Gastrointestinal Tract/metabolism , Hydrogen-Ion Concentration , Medicine, Tibetan Traditional , Mercury/chemistry , Mercury/metabolism , Mercury Compounds/chemistry , Mercury Compounds/metabolism , Water/chemistry , Water/metabolismABSTRACT
Zuotai, a famous Tibetan medicinal mixture containing ß-HgS, has been used to combine with herbal remedies for treating diseases for more than 1 300 years. The target organ for inorganic mercury toxicity is generally considered to be the kidney. Therefore, it is crucial to reveal the chemical speciation, spatial distribution and potential nephrotoxicity of mercury from Zuotai in kidney. To date, this remains poorly understood. We used X-ray absorption spectroscopy (XAS) and micro X-ray fluorescence (µ-XRF) imaging based on synchrotron radiation to study mercury chemical forms and mercury special distribution in kidney after mice were treated orally with Zuotai, ß-HgS or HgCl2. Meanwhile, the histopathology of kidney was observed. Mice exposed with Zuotai showed kidney with significant proportion of mercury ions bound to sulfydryl biomolecules (e.g. Cys-S-Hg-S-Cys) plus some of unknown species, but without methylmercury cysteine, which is the same as ß-HgS and HgCl2. The mercury is mainly deposited in renal cortex in mouse treated with Zuotai, ß-HgS or HgCl2, but with a low level of mercury in medulla. The total mercury in kidney of mice treated with HgCl2 was much higher than that of ß-HgS, and the later was higher than that of Zuotai. And, HgCl2 cause severe impairments in mouse kidney, but that was not observed in the Zuotai and ß-HgS groups. Meanwhile, the bio-metals (Ca, Zn, Fe and Cu) micro-distributions in kidney were also revealed. These findings elucidated the chemical nature, spatial distribution and toxicity difference of mercury from Zuotai, ß-HgS and HgCl2 in mouse kidney, and provide new insights into the appropriate methods for biological monitoring.
Subject(s)
Kidney/drug effects , Mercuric Chloride/adverse effects , Mercury Compounds/adverse effects , Animals , Mercuric Chloride/analysis , Mercury Compounds/analysis , MiceABSTRACT
BACKGROUND: There is limited evidence from nationally representative samples about changes in prescription drug use for financial reasons among cancer survivors in the United States. METHODS: The 2011 to 2014 National Health Interview Survey was used to identify adults who reported ever having been told they had cancer (cancer survivors; n = 8931) and individuals without a cancer history (n = 126,287). Measures of changes in prescription drug use for financial reasons included: 1) skipping medication doses, 2) taking less medicine, 3) delaying filling a prescription, 4) asking a doctor for lower cost medication, 5) buying prescription drugs from another country, and 6) using alternative therapies. Multivariable logistic regression analyses were controlled for demographic characteristics, number of comorbid conditions, interactions between cancer history and number of comorbid conditions, and health insurance coverage. Main analyses were stratified by age (nonelderly, ages 18-64 years; elderly, ages ≥65 years) and time since diagnosis (recently diagnosed, <2 years; previously diagnosed, ≥2 years). RESULTS: Among nonelderly individuals, both recently diagnosed (31.6%) and previously diagnosed (27.9%) cancer survivors were more likely to report any change in prescription drug use for financial reasons than those without a cancer history (21.4%), with the excess percentage changes for individual measures ranging from 3.5% to 9.9% among previously diagnosed survivors and from 2.6% to 2.7% among recently diagnosed survivors (P < .01). Elderly cancer survivors and those without a cancer history had comparable rates of changes in prescription drug use for financial reasons. CONCLUSIONS: Nonelderly cancer survivors are particularly vulnerable to changes in prescription drug use for financial reasons, suggesting that targeted efforts are needed. Cancer 2017;123:1453-1463. © 2016 American Cancer Society.
Subject(s)
Drug Substitution , Neoplasms/epidemiology , Prescription Drugs/economics , Survivors , Adolescent , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/economics , Comorbidity , Complementary Therapies/economics , Cross-Sectional Studies , Humans , Insurance, Health , Middle Aged , Neoplasms/drug therapy , Surveys and Questionnaires , United States/epidemiology , Young AdultABSTRACT
Eleven new abietane type (1â11), and one new kaurane (12), diterpenes, together with eleven known compounds (13-23), were isolated and identified from the stems of Tripterygium regelii, which has been used as a traditional folk Chinese medicine for the treatment of rheumatoid arthritis in China. The structures of new compounds were characterized by means of the interpretation of high-resolution electrospray ionization mass spectrometry (HRESIMS), extensive nuclear magnetic resonance (NMR) spectroscopic data and comparisons of their experimental CD spectra with calculated electronic circular dichroism (ECD) spectra. Compound 1 is the first abietane type diterpene with an 18â1 lactone ring. Compound 19 was isolated from the plants of the Tripterygium genus for the first time, and compounds 14-17 were isolated from T. regelii for the first time. Triregelin I (9) showed significant cytotoxicity against A2780 and HepG2 with IC50 values of 5.88 and 11.74 µM, respectively. It was found that this compound was inactive against MCF-7 cells. The discovery of these twelve new diterpenes not only provided information on chemical substances of T. regelii, but also contributed to the chemical diversity of natural terpenoids.
Subject(s)
Abietanes/isolation & purification , Diterpenes, Kaurane/isolation & purification , Plant Stems/chemistry , Tripterygium/chemistry , Abietanes/chemistry , Abietanes/pharmacology , Carbon-13 Magnetic Resonance Spectroscopy , Cell Death/drug effects , Cell Line, Tumor , Circular Dichroism , Diterpenes, Kaurane/chemistry , Diterpenes, Kaurane/pharmacology , Humans , Proton Magnetic Resonance SpectroscopyABSTRACT
α-HgS is the main component of traditional Chinese medicine cinnabar, while ß-HgS is the main component of Tibetan medicine Zuotai. However, there was no comparative study on the dissolution and absorption in gastrointestinal tract and bioaccumulation in organs of mercury in Cinnabar, Zuotai, α-HgS and ß-HgS. In this study, the dissolution process of the four compounds in the human gastrointestinal tract was simulated to determine the mercury dissolutions and compare the mercury dissolution of different medicines and the dissolution-promoting capacity of different solutions. To explore the absorption and bioaccumulation of cinnabar and Zuotai in organisms, mice were orally administered with clinical equivalent doses cinnabar and Zuotai. Meanwhile, a group of mice was given α-HgS and ß-HgS with the equivalent mercury with cinnabar, while another group was given ß-HgS and HgCl2 with the equivalent mercury with Zuotai. The mercury absorption and bioaccumulation capacities of different medicines in mice and their mercury bioaccumulation in different tissues and organs were compared. The experimental results showed a high mercury dissolutions of Zuotai in artificial gastrointestinal fluid, which was followed by ß-HgS, cinnabar and α-HgS. As for the mercury absorption and bioaccumulation in mice, HgCl2 was the highest, ß-HgS was the next, and a-HgS was slightly higher than cinnabar. The organs with the mercury bioaccumulation from high to low were kidney, liver and brain. This study is close to clinical practices and can provide reference for the clinical safe medication as well as a study model for the safety evaluation on heavy metal-containing medicines by observing the mercury dissolution, absorption, distribution and accumulation of mercury-containing medicines cinnabar and zuotai.
Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Gastrointestinal Tract/metabolism , Mercury Compounds/pharmacokinetics , Animals , Brain/metabolism , Drugs, Chinese Herbal/chemistry , Kidney/metabolism , Liver/metabolism , Male , Mercury/chemistry , Mercury/pharmacokinetics , Mercury Compounds/chemistry , Mice , SolubilityABSTRACT
Four common traditional tibetan medicine prescription preparations "Anzhijinghuasan, Dangzuo, Renqingchangjue and Rannasangpei" in tibetan areas were selected as study objects in the present study. The purpose was to try to establish a kind of wet digestion and flow injection-hydride generation-atomic absorption spectrometry (FI-HAAS) associated analysis method for the content determinations of lead and arsenic in traditional tibetan medicine under optimized digestion and measurement conditions and determine their contents accurately. Under these optimum operating conditions, experimental results were as follows. The detection limits for lead and arsenic were 0.067 and 0.012 µg · mL(-1) respectively. The quantification limits for lead and arsenic were 0.22 and 0.041 µg · mL(-1) respectively. The linear ranges for lead and arsenic were 25-1,600 ng · mL(-1) (r = 0.9995) and 12.5-800 ng · mL(-1) (r = 0.9994) respectively. The degrees of precision(RSD) for lead and arsenic were 2.0% and 3.2% respectively. The recovery rates for lead and arsenic were 98.00%-99.98% and 96.67%-99.87% respectively. The content determination results of lead and arsenic in four traditional tibetan medicine prescription preparations were as fol- lows. The contents of lead and arsenic in Anzhijinghuasan are 0.63-0.67 µg · g(-1) and 0.32-0.33 µg · g(-1) in Anzhijinghua- san, 42.92-43.36 µg · g(-1) and 24.67-25.87 µg · g(-1) in Dangzuo, 1,611. 39-1,631.36 µg · g(-1) and 926.76-956.52 µg- g(-1) in Renqing Changjue, and 1,102.28-1,119.127 µg-g(-1) and 509.96-516.87 µg · g(-1) in Rannasangpei, respectively. This study established a method for content determination of lead and arsenic in traditional tibetan medicine, and determined the content levels of lead and arsenic in four tibetan medicine-prescription preparations accurately. In addition, these results also provide the basis for the safe and effective use of those medicines in clinic.
Subject(s)
Arsenic/analysis , Drug Contamination , Lead/analysis , Medicine, Tibetan Traditional , Spectrophotometry, AtomicABSTRACT
Zuotai (gTso thal) is a typical representative of Tibetan medicines containing heavy metals, but there is still lack of modem safety evaluation data so far. In this study, acute toxicity test, sub-acute toxicity test, one-time administration mercury distribution experiment, long-term mercury accumulative toxicity experiment and preliminary study on clinical safety of Compound Dangzuo were conducted in the hope of obtain the medicinal safety data of Zuotai. In the acute toxicity test, half of KM mice given the lethal dose of Zuotai were not died or poisoned, and LD50 was not found. The maximum tolerated dose of Zuotai was 80 g x kg(-1). In the subacute toxicity test, Zuotai could reduce ALT, AST, Crea levels in serums under low dose (13.34 mg x kg(-1) x d(-1)) and medium dose (53.36 mg x kg(-1) x d(-1)), with significant difference under low dose, and increase the levels of ALT, AST, MDA, Crea in serums under high dose (2 000 mg x kg(-1) x d(-1)); besides, the levels of BUN and GSH in serums reduced with the increase in dose of Zuotai, indicating a significant dose-effect relationship. In the one-time administration distribution experiment, the content of mercury in rat kidney, liver and lung increased after the one-time administration with Zuotai, with a significant dose-dependent relationship in kidney. In the long-term mercury accumulative toxicity experiment, KM mice were administered with equivalent doses of Zuotai for 4.5 months and then stopped drug administration for 1.5 months. Since the 2.5th month, they showed significant mercury accumulation in kidney, which gradually reduced after drug withdrawal, without significant change in mercury content in liver, spleen and brain and ALT, AST, TBIL, BUN and Crea in serum. At the 4.5th month after drug administration, KM mice showed slight structural changes in kidney, liver and spleen tissues, and gradually recovered to normal after drug withdrawal. Besides, no significant difference in weight gain was found between the Zuotai group and the control group. According to the findings of the clinical safety study of Dangzuo, after subjects administered Dangzuo under clinical dose for one month, their serum biochemical indicators, blood routine indicators and urine routine indicators showed no significant adverse change. This study proved that traditional Tibetan medicine Zuotai was slightly toxic, with a better safety in clinical combined administration and no adverse effects on bodies under the clinical dose and clinical medication cycle. However, long-term high-dose administration of Zuotai may have a certain effect on kidney.