1.Hypolipidemic effect and mechanism of Arisaema Cum Bile based on gut microbiota and metabolomics.
Peng ZHANG ; Fa-Zhi SU ; En-Lin ZHU ; Chen-Xi BAI ; Bao-Wu ZHANG ; Yan-Ping SUN ; Hai-Xue KUANG ; Qiu-Hong WANG
China Journal of Chinese Materia Medica 2025;50(6):1544-1557
Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals
;
Gastrointestinal Microbiome/drug effects*
;
Rats
;
Male
;
Metabolomics
;
Hyperlipidemias/microbiology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Rats, Sprague-Dawley
;
Hypolipidemic Agents/pharmacology*
;
Liver/metabolism*
;
Humans
;
Alanine Transaminase/metabolism*
;
Triglycerides/metabolism*
;
Aspartate Aminotransferases/metabolism*
2.The Correlation between miR451a and Occult Hepatitis B Virus Infection in Voluntary Blood Donors.
Qiang LIU ; Wei YU ; Fang WANG
Journal of Experimental Hematology 2025;33(2):546-551
OBJECTIVE:
To analyze the relationship between miR451a and occult hepatitis B virus infection (OBI) in voluntary blood donors, and to provide ideas for the identification of OBI.
METHODS:
A total of 125 003 blood samples were collected from voluntary blood donors in our center from January 2022 to June 2023, and OBI infection was detected by blood screening. At the same time, 40 HBsAg double reagent reactive samples (S/CO>3.0) were selected as the positive control group, and 40 healthy blood donors were selected as the negative control group (normal group). The plasma miR451a level was detected, and the serum indexes of total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST). The relationship between miR451a and OBI were analyzed.
RESULTS:
54 out of 125 003 blood samples were diagnosed as OBI, and the OBI infection rate was 0.043% (54/125 003). Compared with the normal group, the relative expression of plasma miR451a in the OBI group and the positive control group was down-regulated (P < 0.05), but there was no significant difference in the relative expression of plasma miR451a between the OBI group and the positive control group (P >0.05). The HBV DNA load, TBil, ALT and AST levels in the positive control group were higher than those in the OBI group and the normal group (P < 0.05). There was no significant difference in plasma TBil, ALT and AST levels between OBI group and normal group (P >0.05). Logistic regression analysis and receiver operating curve (ROC) showed that plasma miR451a could distinguish OBI group from healthy group, and the area under the curve (AUC) was 0.904 (95%CI : 0.829-0.978). However, plasma miR451a was difficult to distinguish between OBI and HBsAg responders.
CONCLUSION
Plasma miR451a can be used as a potential biomarker for HBV infection, and can be used to identify OBI in HBsAg non-reactive blood donors.
Humans
;
MicroRNAs/blood*
;
Blood Donors
;
Hepatitis B/blood*
;
Hepatitis B virus
;
Alanine Transaminase/blood*
;
Aspartate Aminotransferases/blood*
;
Female
;
Male
;
Adult
;
Hepatitis B Surface Antigens/blood*
3.Early liver injury risk assessment in critically injured trauma patients using intelligent calculation method: a retrospective study.
Xiaoming HOU ; Wenjun ZHAO ; Wenhua LI ; Xiaomei WANG ; Baoqi ZENG ; Xiaozhi LIU ; Qingguo FENG ; Bo KANG ; Na XUE
Chinese Critical Care Medicine 2025;37(2):165-169
OBJECTIVE:
To explore the early changes in various liver function indicators in critically injured trauma patients assessed by intelligent calculation method, aiming to develop more advantageous diagnostic and treatment strategies for traumatic liver injury.
METHODS:
A retrospective study was conducted. Critically injured trauma patients [injury severity score (ISS) ≥ 16, age > 18 years old] admitted to the Emergency Medical Center of Tianjin Fifth Central Hospital from January 1, 2022, to December 1, 2023 were enrolled. ISS score and acute physiology and chronic health evaluation II (APACHE II) assessed by intelligent calculation method were collected upon patient admission to the emergency medical center. Trends in liver function indicators in fasting venous serum were analyzed at 6, 24 and 72 hours after admission, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), albumin (ALB), total bilirubin (TBil), prothrombin time (PT). Patients were grouped based on APACHE II scores into those with APACHE II < 15 and APACHE II ≤ 15, and liver function indicators within 6 hours of admission were compared between the two groups.
RESULTS:
A total of 112 critically injured trauma patients were included, with 83 males and 29 females, an average age of (47.78±14.84) years old. The median ISS score was 21.0 (18.0, 26.0). The most common cause of injury for critically injured trauma patients was road traffic accidents (68 cases, accounting for 60.71%), followed by falls from heights, compression injuries, heavy object injuries, knife stabs, and explosion injuries. The most common injured areas was the limbs and pelvis (97 cases, accounting for 86.61%), followed by chest injuries, surface skin and soft tissue injuries, abdominal and pelvic organ injuries, head injuries, and facial injuries. The proportion of elevated LDH, AST, and ALT within 6 hours of admission was 77.68%, 79.46%, and 52.68%, respectively, while the proportion of decreased ALB was 75.89%, the abnormal rates of ALP, GGT, TBil, and PT were all below 50%. The ALT and AST levels of patients at 24 hours and 72 hours after admission were significantly lower than those at 6 hours after admission [ALT (U/L): 37.0 (22.0, 66.0), 31.0 (21.2, 52.0) vs. 41.0 (25.0, 71.0), AST (U/L): 55.5 (30.0, 93.5), 40.0 (27.0, 63.2) vs. 69.5 (39.0, 130.8), all P < 0.05]. There was no statistically significant difference in ISS score between APACHE II > 15 group (45 cases) and APACHE II ≤ 15 group [67 cases; 21.0 (18.5, 26.5) vs. 20.0 (17.0, 22.0), P > 0.05]. Nevertheless, compared with patients with APACHE II ≤ 15, patients with APACHE II > 15 have a higher abnormality rate of ALT and AST within 6 hours of admission [ALT abnormal rate: 66.44% (29/45) vs. 44.78% (30/67), AST abnormal rate: 93.33% (42/45) vs. 70.15% (47/67), both P < 0.05], and the levels of ALT and AST were higher [ALT (U/L): 56.0 (30.0, 121.0) vs. 35.0 (21.0, 69.0), AST (U/L): 87.0 (48.0, 233.0) vs. 52.0 (31.0, 117.0), both P < 0.05].
CONCLUSIONS
Severe trauma patients frequently exhibit a high incidence of reversible early liver function impairment. Based on intelligent calculation method, the utilization of both the ISS and APACHE II scores demonstrates a distinct advantage in the assessment of their early liver injury.
Humans
;
Retrospective Studies
;
Liver/physiopathology*
;
Risk Assessment
;
APACHE
;
Wounds and Injuries
;
Adult
;
Injury Severity Score
;
Male
;
Middle Aged
;
Female
;
Liver Function Tests
;
Alanine Transaminase/blood*
;
Young Adult
;
Aspartate Aminotransferases/blood*
4.Increase in transaminase levels during COVID-19 infection and its association with poor prognosis.
Oguz Kagan BAKKALOGLU ; Ugur ONAL ; Tugce ESKAZAN ; Enes Ali KURT ; Selcuk CANDAN ; Ridvan KARAALI ; Sermin BOREKCI ; Seval URKMEZ ; Yalim DIKMEN ; Fehmi TABAK ; Murat TUNCER ; Ibrahim HATEMI
Singapore medical journal 2023;64(10):640-644
5.Precise application of Beichaihu and Nanchaihu in classical formulas.
Yu-Ping SHE ; Pei-Pei ZHANG ; Jing-Yan HU ; Yong-Hua GUO ; Qian CAO ; Xiang YIN ; Xiu-Hua HU ; Ting ZHAO ; Feng-Bo LIU ; Yuan ZHANG ; Sheng-Li WEI
China Journal of Chinese Materia Medica 2023;48(3):681-688
To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.
Animals
;
Mice
;
Liver
;
Aspartate Aminotransferases
;
Bupleurum
6.Application of a low copper diet guidance based on food exchange portions in children with hepatolenticular degeneration.
Ying-Xiang CHEN ; Zheng-Qing QIU ; Jing SUN ; Yang LI ; Ying YANG
Chinese Journal of Contemporary Pediatrics 2023;25(6):612-618
OBJECTIVES:
To study the efficacy of a low-copper diet guidance based on food exchange portions in children with hepatolenticular degeneration.
METHODS:
A self-controlled study was conducted from July 2021 to June 2022, including 30 children under the age of 18 who were diagnosed with hepatolenticular degeneration and poorly controlled with a low-copper diet. During the medical visit, personalized low-copper diet guidance was provided to the children and their parents using a copper-containing food exchange table and a copper food exchange chart. During home care, compliance with the low-copper diet of the children was improved by recording dietary diaries and conducting regular follow-ups. The changes in 24-hour urine copper level, liver function indicators, and the low-copper diet knowledge of the children's parents were observed before and after the intervention, with no change in the original drug treatment.
RESULTS:
After 8, 16, and 24 weeks of intervention, the 24-hour urine copper level decreased significantly compared to before intervention (P<0.05). When compared to 8-week intervention, the urine copper level decreased significantly after 16 and 24 weeks of intervention. The 24-hour urine copper level after 24 weeks of intervention decreased significantly compared to 16 weeks of intervention (P<0.05).After 24 weeks of intervention, the alanine aminotransferase and aspartate aminotransferase levels decreased significantly compared to before intervention (P<0.05). Additionally, in 16 of the cases (53%), alanine aminotransferase and aspartate aminotransferase returned to normal levels. Following 8 weeks of intervention, the low-copper diet knowledge of the children's parents increased significantly (P<0.05).
CONCLUSIONS
A low-copper diet guidance based on food exchange portions can effectively decrease the urine copper level and improve liver function in children with hepatolenticular degeneration. Furthermore, it can increase the low-copper diet knowledge of the children's parents.
Humans
;
Child
;
Hepatolenticular Degeneration/therapy*
;
Alanine Transaminase
;
Copper
;
Food
;
Aspartate Aminotransferases
7.Effects of Li-Dan-He-Ji on regulating oxidative stress and antagonising infantile cholestatic hepatic fibrosis.
Wei YI ; Suqi YAN ; Jianqiao TANG ; Xiang MA ; Mengjie SU ; Hong LI
Chinese Critical Care Medicine 2023;35(7):741-745
OBJECTIVE:
To explore the clinical effect of Li-Dan-He-Ji in the treatment of infantile cholestatic hepatic fibrosis.
METHODS:
Patients who met the diagnostic criteria of infantile cholestatic hepatic fibrosis in the department of integrated traditional Chinese and Western medicine and the department of gastroenterology of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to December 2021 were included in the study by prospective randomized controlled trial. They were divided into the conventional treatment group and Li-Dan-He-Ji group according to the random number table. The patients in the conventional treatment group were given conventional treatment according to the guidelines. In the Li-Dan-He-Ji group, the self-made Chinese medicinal compound Li-Dan-He-Ji (prescription: Herba Artemisiae Scopariae, Fructus Forsythiae, Radix et Rhizoma Rhei preparata, Radix Polygoni Multiflori Preparata, Radix Paeoniae Rubra, Ramulus Cinnamomi, Fructus Aurantii, Rhizoma Atractylodis Macrocephalae, Fructus Schisandrae Chinensis, Carapax Trionycis, and Radix Glycyrrhizae) was given on the basis of the routine treatment, by oral, enema or nasal feeding, 60 mL each day, divided into 2 or 3 times, for 28 days. Outpatient follow-up was maintained for 4 weeks. Before and after treatment, serum liver fibrosis 4 items [type IV collagen (IV-C), hyaluronidase (HA), type III procollagen (PC III), laminin (LN)], liver function and cholestasis-related markers [total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)], liver stiffness measurement (LSM) detected by transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and liver and spleen retraction time were recorded in the two groups.
RESULTS:
During the observation period, a total of 40 cases of cholestatic hepatic fibrosis were treated, including 21 cases in the conventional treatment group and 19 cases in the Li-Dan-He-Ji group. Before treatment, the differences in serum liver fibrosis 4 items, serum liver function and cholestasis-related markers, oxidative stress indexes, LSM and APRI of the two groups were not statistically significant. After treatment, the liver fibrosis 4 items, liver function and cholestasis-related markers, LSM, and APRI were all significantly decreased in both groups, and the indexes in the Li-Dan-He-Ji group were significantly lower than those in the conventional treatment group [HA (ng/L): 165.81±21.57 vs. 203.87±25.88, PC III (μg/L): 69.86±9.32 vs. 81.82±7.39, IV-C (μg/L): 204.14±38.97 vs. 239.08±24.93, LN (μg/L): 162.40±17.39 vs. 190.86±15.97, TBil (μmol/L): 37.58±27.63 vs. 53.06±45.09, DBil (μmol/L): 20.55±19.34 vs. 30.08±27.39, ALP (U/L): 436.50±217.58 vs. 469.60±291.69, γ-GGT (U/L): 66.78±35.84 vs. 87.00±32.82, ALT (U/L): 64.75±50.53 vs. 75.20±50.19, AST (U/L): 77.25±54.23 vs. 96.80±59.77, TBA (μmol/L): 74.35±44.44 vs. 85.45±39.50, LSM (kPa): 5.24±0.39 vs. 7.53±3.16, APRI: 0.52±0.39 vs. 0.98±0.29, all P < 0.05]. After treatment, MDA in the two groups were significantly lower than those before treatment, and SOD and GSH were significantly higher than those before treatment. The level of SOD in the Li-Dan-He-Ji group was significantly higher than that in the conventional treatment group (kU/L: 64.56±6.69 vs. 51.58±5.98, P < 0.05). In addition, the liver retraction time (day: 20.13±10.97 vs. 24.33±13.46) and spleen retraction time (day: 25.93±13.01 vs. 29.14±14.52) in the Li-Dan-He-Ji group were significantly shorter than those in the conventional treatment group (both P < 0.05).
CONCLUSIONS
The use of Li-Dan-He-Ji in the treatment of cholestatic hepatic fibrosis can effectively improve the indicators of cholestasis, hepatic fibrosis, oxidative stress and clinical symptoms in children.
Child
;
Humans
;
Prospective Studies
;
Cholestasis/pathology*
;
Liver
;
Liver Cirrhosis/drug therapy*
;
Bilirubin/pharmacology*
;
Oxidative Stress
;
Aspartate Aminotransferases/metabolism*
;
Superoxide Dismutase/metabolism*
8.Deficiency in glutathione synthesis and reduction contributes to the pathogenesis of colitis-related liver injury.
Liangliang WANG ; Ruyue HAN ; Kaihong ZANG ; Pei YUAN ; Hongyan QIN
Journal of Central South University(Medical Sciences) 2022;47(3):271-279
OBJECTIVES:
Liver disease is the most common extra-intestinal manifestation of ulcerative colitis (UC), but the underlying pathogenesis is still not clarified. It is well accepted that the occurrence of UC-related liver disease has close correlation with immune activation, intestinal bacterial liver translocation, inflammatory cytokine storm, and the disturbance of bile acid circulation. The occurrence of UC-related liver disease makes the therapy difficult, therefor study on the pathogenesis of UC-related liver injury is of great significance for its prevention and treatment. Glutathione (GSH) shows multiple physiological activities, such as free radical scavenging, detoxification metabolism and immune defense. The synthesis and the oxidation-reduction all contribute to GSH antioxidant function. It is reported that the deficiency in hepatic GSH antioxidant function participates in multiple liver diseases, but whether it participates in the pathogenesis of UC-related liver injury is still not clear. This study aims to investigate the feature and underlying mechanism of GSH synthesis and oxidation-reduction function during the development of UC, which will provide useful information for the pathogenesis study on UC-related liver injury.
METHODS:
UC model was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS)-ethanol solution (5 mg/0.8 mL per rat, 50% ethanol) via intra-colonic administration in rats, and the samples of serum, liver, and colon tissue of rats were collected at the 3rd, 5th, and 7th days post TNBS. The severity degree of colitis was evaluated by measuring the disease activity index, colonic myeloperoxidase activity, and histopathological score, and the degree of liver injury was evaluated by histopathological score and the serum content of alanine aminotransferase. Spearman correlation analysis was also conducted between the degree of colonic lesions and index of hepatic histopathological score as well as serum aspartate aminotransferase level to clarify the correlation between liver injury and colitis. To evaluate the hepatic antioxidant function of GSH in UC rats, hepatic GSH content, enzyme activity of GSH peroxidase (GSH-Px), and GSH reductase (GR) were determined in rats at the 3rd, 5th, and 7th days post TNBS, and the protein expressions of glutamine cysteine ligase (GCL), GSH synthase, GSH-Px, and GR in the liver of UC rats were also examined by Western blotting.
RESULTS:
Compared with the control, the disease activity index, colonic myeloperoxidase activity, and histopathological score were all significantly increased at the 3rd, 5th, and 7th days post TNBS (all P<0.01), the serum aspartate aminotransferase level and hepatic histopathologic score were also obviously elevated at the 7th day post TNBS (all P<0.05). There was a significant positive correlation between the degree of liver injury and the severity of colonic lesions (P=0.000 1). Moreover, compared with the control, hepatic GSH content and the activity of GSH-Px and GR were all significantly decreased at the 3rd and 5th days post TNBS (P<0.05 or P<0.01), and the protein expressions of GCL, GSH-Px, and GR were all obviously down-regulated at the 3rd, 5th, and 7th days post TNBS (P<0.05 or P<0.01).
CONCLUSIONS
There is a significant positive correlation between the degree of liver injury and the severity of colonic lesions, and the occurrence of reduced hepatic GSH synthesis and decreased GSH reduction function is obviously earlier than that of the liver injury in UC rats. The reduced hepatic expression of enzymes that responsible for GSH synthesis and reduction may contribute to the deficiency of GSH synthesis and oxidation-reduction function, indicating that the deficiency in GSH antioxidant function may participate in the pathogenesis of UC related liver injury.
Animals
;
Antioxidants
;
Aspartate Aminotransferases
;
Colitis/chemically induced*
;
Colitis, Ulcerative/metabolism*
;
Colon/pathology*
;
Glutathione/biosynthesis*
;
Liver/metabolism*
;
Peroxidase/metabolism*
;
Rats
;
Trinitrobenzenesulfonic Acid
9.Quantitative Assessment of Dentine Sialophosphoprotein, Aspartate Aminotransferase and Lactate Dehydrogenase in Gingival Crevicular Fluid of Teeth with Root Resorption
Noor Ayuni Ahmad Shafiai ; Rohaya Megat Abdul Wahab
Archives of Orofacial Sciences 2022;17(2):237-246
ABSTRACT
Root resorption is a shortening of root dentine which occurs physiologically in deciduous teeth. The
present study aimed to quantify dentine sialophosphoprotein (DSPP), aspartate aminotransferase (AST)
and lactate dehydrogenase (LDH) in gingival crevicular fluid (GCF) during the physiological process
of root resorption of deciduous teeth. A cross-sectional study was conducted with 25 children aged
between 4 and 10 years old. GCF was collected from the gingival sulcus using periopaper strips from the
upper first deciduous molar (n = 45). The samples were divided equally into three groups, no resorption
(R0), moderate resorption (RM) and severe resorption (RS), based on the existing radiographs taken.
The GCF samples were then analysed using an enzyme-linked immunosorbent assay (ELISA) kit
to determine the DSPP concentration levels and BioAssays System kit for AST and LDH. One-way
ANOVA was used to determine the statistical differences between the means of the DSPP, AST and
LDH concentration level in the three groups. A difference was considered significant when p < 0.05.
High concentration levels of DSPP were significantly noted in RS (p < 0.05), compared to RM and
R0. AST also portrayed significant high activity level (p < 0.05) similar to DSPP but LDH showed no
significant changes between groups (p > 0.05). The high quantification of DSPP and AST levels in
the severe and moderately resorbed roots indicated the potential use of this protein as a biomarker for
detecting moderate-severe stages of root resorption.
Root Resorption
;
Gingival Crevicular Fluid
;
Dentin
;
Aspartate Aminotransferases
;
Lactate Dehydrogenases
10.Preparation of salvianolic acid B, tanshinone Ⅱ_A, and glycyrrhetinic acid lipid emulsion and its protective effect against acute liver injury induced by acetaminophen.
Xiu-Rong ZHANG ; Tao LIN ; Xiu-Li WANG ; Xiao-Jie WANG ; Heng GU
China Journal of Chinese Materia Medica 2022;47(17):4634-4642
Salvianolic acid B(Sal B), tanshinone Ⅱ_A(TSN Ⅱ_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.
Abietanes/therapeutic use*
;
Acetaminophen/therapeutic use*
;
Alanine Transaminase/metabolism*
;
Animals
;
Antipyretics/therapeutic use*
;
Aspartate Aminotransferases/metabolism*
;
Benzofurans/therapeutic use*
;
Chemical and Drug Induced Liver Injury/prevention & control*
;
Depsides/therapeutic use*
;
Emulsions
;
Glycyrrhetinic Acid/therapeutic use*
;
Liver/drug effects*
;
Malondialdehyde
;
Mice


Result Analysis
Print
Save
E-mail