A clinical experience-based Chinese herbal formula improves ethanol-induced drunken behavior and hepatic steatohepatitis in mice modelsChinese Medicine - Tập 18 Số 1
Han Gao, Zhen Li, Yao Liu, Yong-kang Zhao, Cheng Cheng, Feng Qiu, Yuan Gao, Ya-wen Lu, Xin-hua Song, Jiabo Wang, Zhi-tao Ma
Abstract
Background
Bao-Gan-Xing-Jiu-Wan (BGXJW) is a clinical experience-based Chinese herbal formula. Its efficacy, pharmacological safety, targeted function, process quality, and other aspects have met the evaluation standards and the latest requirements of preparations. It could prevent and alleviate the symptoms of drunkenness and alcoholic liver injury clinically. The present work aims to elucidate whether BGXJW could protect against drunkenness and alcoholic liver disease in mice and explore the associated mechanism.
Material and methods
We used acute-on-chronic (NIAAA) mice model to induce alcoholic steatosis, and alcohol binge-drinking model to reappear the drunk condition. BGXJW at indicated doses were administered by oral gavage respectively to analyze its effects on alcoholic liver injury and the associated molecular mechanisms.
Results
BGXJW had no cardiac, hepatic, renal, or intestinal toxicity in mice. Alcoholic liver injury and steatosis in the NIAAA mode were effectively prevented by BGXJW treatment. BGXJW increased the expression of alcohol metabolizing enzymes ADH, CYP2E1, and ALDH2 to enhance alcohol metabolism, inhibited steatosis through regulating lipid metabolism, counteracted alcohol-induced upregulation of lipid synthesis related proteins SREBP1, FASN, and SCD1, meanwhile it enhanced fatty acids β-oxidation related proteins PPAR-α and CPT1A. Alcohol taken enhanced pro-inflammatory TNF-α, IL-6 and down-regulated the anti-inflammatory IL-10 expression in the liver, which were also reversed by BGXJW administration. Moreover, BGXJW significantly decreased the blood ethanol concentration and alleviated drunkenness in the alcohol binge-drinking mice model.
Conclusions
BGXJW could effectively relieve drunkenness and prevent alcoholic liver disease by regulating lipid metabolism, inflammatory response, and alcohol metabolism.
Graphical Abstract
Radix Puerariae lobatae (Gegen) suppresses the anticoagulation effect of warfarin: a pharmacokinetic and pharmacodynamics studyChinese Medicine - Tập 11 - Trang 1-17 - 2016
Beikang Ge, Zhen Zhang, Zhong Zuo
Radix Salvia miltiorrhiza (Danshen) and Radix Puerariae lobatae (Gegen) are used in Traditional Chinese Medicine to treat cardiovascular diseases. However, adverse herb-drug interactions were observed between warfarin and herbal remedies containing Danshen and Gegen. This study aims to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and the different components found in Danshen and Gegen. Sixty Sprague–Dawley rats were used to investigate the effects of warfarin (0.2 mg/kg), Danshen (240 or 480 mg/kg) and Gegen (240 or 480 mg/kg) both in isolation and combination. The rats in the warfarin and Danshen/Gegen combination groups were given an oral dose of Danshen or Gegen 2 h after being given an oral dose of warfarin. After five consecutive days of treatment, the pharmacokinetic interactions between Danshen/Gegen and warfarin were investigated by simultaneously monitoring and comparing the cytochrome P450 (CYP) activities, mRNA and protein expression levels in the livers of the rats from the different treatment groups. The pharmacodynamic interactions were evaluated by monitoring and comparing the vitamin K epoxide reductase (VKOR) activities, mRNA and protein expression levels in the livers of rats from the different groups, as well as the thrombomodulin (TM) activities, mRNA and protein in the lungs of these animals. The rat plasma soluble thrombomodulin concentrations of the different treatment groups were also evaluated. Microsomes incubation, Real Time-Polymerase Chain Reaction and Western blot was applied respectively to study the activity, mRNA expression and protein expression of CYP, VKOR and TM. The activities and expression levels of the CYP and VKOR enzymes in the warfarin-Gegen combination groups increased by nearly 30 % (P = 0.02) compared with the warfarin-alone group, whereas those of TM decreased by almost 25 % (P = 0.02). The administration of Danshen did not lead to any changes in the activities or the expression levels of the CYP, VKOR or TM enzymes compared with those of the control group. Gegen induced several warfarin-metabolizing CYP enzymes and neutralized the effects of warfarin towards VKOR and TM.
Gegen, rather than Danshen at the same tested dosage, offsets the anticoagulant effects of warfarin by accelerating the phase I liver metabolism of warfarin, as well as increasing the activity, mRNA and protein expression of VKOR while decreasing those of TM.
Novel phthalide derivatives identified from Ligusticum chuanxiong (Chuanxiong)Chinese Medicine - Tập 11 - Trang 1-7 - 2016
Jun Yang, Xiao-Lin Feng, Yang Yu, Qi Wang, Jian Zou, Chuan-Xi Wang, Zhen-Qiang Mu, Xin-Sheng Yao, Hao Gao
Ligusticum chuanxiong Hort. (Chuanxiong) is a well-known Chinese medicine, and studies on its chemical constituents are important for explaining its mechanism of action and quality control. This study aims to investigate the chemical constituents of the dried rhizome of. L. chuanxiong.
The dried rhizome of L. chuanxiong was extracted with 60 % ethanol, and the concentrated extract was isolated by silica gel, octadecyl silane, and Sephadex LH-20 columns, followed by preparative/semipreparative high-performance liquid chromatography (HPLC) to obtain the pure chemical constituents. The structures of the constituents were elucidated by HR-ESI-MS, UV, IR, 1D NMR, and 2D NMR methods. Enantiomeric separation was achieved by a chiral HPLC method. The absolute configuration was determined by the modified Mosher’s method. Six novel phthalide derivatives, (+)/(−)-chuanxiongins A–F (1–6), together with four known phthalides (7–10) were isolated from Chuanxiong. All of the new compounds (1–6) were present as pairs of enantiomers. Enantiomeric separation of 1 was successfully achieved by HPLC on a chiral column. The absolute configuration of (−)-1 was determined by a modified Mosher’s method. The six novel phthalide derivatives (1–6) isolated from Chuanxiong were phthalide fatty acid esters that were structurally analogous and characterized by fatty acid acylation at 6-OH or 7-OH.
Metabonomic study of the protective effect of Fukeqianjin formula on multi-pathogen induced pelvic inflammatory disease in ratsChinese Medicine - Tập 13 - Trang 1-13 - 2018
Yan Zhang, Wei Li, Liang Zou, Yun Gong, Peng Zhang, Shasha Xing, Hang Yang
Fukeqianjin formula has been effectively used in the treatment of pelvic inflammatory disease (PID) and the related complications in clinic. Although there have been some studies about the underlying mechanism that focus on its anti-inflammatory and immunoregulatory activities. But the mechanism is still not fully understood. The aim of this study was to investigate the alteration of plasma metabolic profiles in PID rats and the regulatory effect of Fukeqianjin formula on potential biomarkers. Pelvic inflammatory model was established by intrauterine inoculation of multiple pathogens combined with mechanical injury of endometrium. Rats were randomly divided into normal group, model group, azithromycin group, high-and low-dose of Fukeqianjin formula treatment group (FF-H, and FF-L, respectively). After 14 days of intragastric administration, the plasm levels of interleukin-1β (IL-1β) and nitric oxide (NO) were measured. To further recognize and identify potential biomarkers and metabolic pathways, an ultra-performance liquid chromatography-quadrupole-Exactive Orbitrap-mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) metabonomic method combined with multivariate analyses including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA), was employed to analyze the metabolic profiling. Compared with normal group, the plasma levels of IL-1β and NO were significantly increased in the PID model group (P < 0. 05), and obviously decreased after high-dose intervention of Fukeqianjin formula (P < 0. 01). The PCA, PLS-DA and OPLS-DA analysis showed that PID rats were clearly separated from normal rats. Compared with the PID model group, the metabolite profiles of Fukeqianjin formula treatment group was gradually restored to normal. Meanwhile, 14 potential metabolite biomarkers, which were mainly related to the metabolic pathways of intervening glycerophospholipid metabolism, linoleic acid metabolism/alpha-linolenic acid metabolism, amino acid metabolism, arachidonic acid metabolism, and unsaturated fatty acids biosynthesis, have been identified. Fukeqianjin formula exerts good regulatory effect on the abnormal metabolism of PID rats. Intrauterine inoculation of multiple pathogens combined with mechanical injury of endometrium could significantly disturb the plasma metabolic profiles of rats. Fukeqianjin formula has potential therapeutic effect on multi-pathogen-induced PID by ameliorating metabolism disorders and alleviating the inflammatory response.
Regulation of polysaccharide in Wu‐tou decoction on intestinal microflora and pharmacokinetics of small molecular compounds in AIA ratsChinese Medicine - Tập 19 - Trang 1-13 - 2024
Di Yang, Xiaoxu Cheng, Meiling Fan, Dong Xie, Zhiqiang Liu, Fei Zheng, Yulin Dai, Zifeng Pi, Hao Yue
Wu-tou decoction (WTD), a traditional Chinese medicine prescription, is used to treat rheumatoid arthritis (RA). It works by controlling intestinal flora and its metabolites, which in turn modulates the inflammatory response and intestinal barrier function. Small molecular compounds (SM) and polysaccharides (PS) were the primary constituents of WTD extract. In this work, a model of adjuvant-induced arthritis (AIA) in rats was established and treated with WTD, SM, and PS, respectively. 16S rRNA gene sequencing was used to examine the regulatory impact of the various groups on the disturbance of the gut flora induced by RA. Further, since PS cannot be absorbed into the blood, the influence of PS on the absorption and metabolism of SM was studied by examining their pharmacokinetic (PK) parameters of 23 active components in SM by UPLC-MS/MS. WTD was found to be more effective than PS and SM in alleviating arthritis in AIA rats, which may be related to changes in gut flora. The PK properties of 13 active compounds were altered after PS intervene. Based on the findings, PS may be able to manage the disruption of intestinal microbiota, enhance the intestinal environment of model animals, and hence influence SM absorption and metabolism.
SKP alleviates the ferroptosis in diabetic kidney disease through suppression of HIF-1α/HO-1 pathway based on network pharmacology analysis and experimental validationChinese Medicine - - 2024
Yangtian Yan, Ningning Yuan, Yuchi Chen, Yun Ma, Ali Chen, Fujing Wang, Shihua Yan, Zhuo’en He, Jinyue He, Chi Zhang, Hao Wang, Mingqing Wang, Jianxin Diao, Wei Xiao
Diabetic kidney disease (DKD) represents a microvascular complication of diabetes mellitus. Shenkang Pills (SKP), a traditional Chinese medicine formula, has been widely used in the treatment of DKD and has obvious antioxidant effect. Ferroptosis, a novel mode of cell death due to iron overload, has been shown to be associated with DKD. Nevertheless, the precise effects and underlying mechanisms of SKP on ferroptosis in diabetic kidney disease remain unclear. The active components of SKP were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Protein–protein interaction (PPI) network and Herb-ingredient-targets gene network were constructed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted utilizing the Metascape system database. Additionally, an in vivo model of DKD induced by Streptozotocin (STZ) was established to further investigate and validate the possible mechanisms underlying the effectiveness of SKP. We retrieved 56 compounds and identified 223 targets of SKP through the TCMSP database. Key targets were ascertained using PPI network analysis. By constructing a Herb-Ingredient-Targets gene network, we isolated the primary active components in SKP that potentially counteract ferroptosis in diabetic kidney disease. KEGG pathway enrichment analysis suggested that SKP has the potential to alleviate ferroptosis through HIF signaling pathway, thereby mitigating renal injury in DKD. In animal experiments, fasting blood glucose, 24 h urine protein, urea nitrogen and serum creatine were measured. The results showed that SKP could improve DKD. Results from animal experiments were also confirmed the efficacy of SKP in alleviating renal fibrosis, oxidative stress and ferroptosis in DKD mice. These effects were accompanied by the significant reductions in renal tissue expression of HIF-1α and HO-1 proteins. The mRNA and immunohistochemistry results were the same as above. SKP potentially mitigating renal injury in DKD by subduing ferroptosis through the intricacies of the HIF-1α/HO-1 signaling pathway.
An anti-inflammatory and anti-fibrotic proprietary Chinese medicine nasal spray designated as Allergic Rhinitis Nose Drops (ARND) with potential to prevent SARS-CoV-2 coronavirus infection by targeting RBD (Delta)- angiotensin converting enzyme 2 (ACE2) bindingChinese Medicine - Tập 17 - Trang 1-20 - 2022
Ka Man Yip, Kwan Ming Lee, Tzi Bun Ng, Shujun Xu, Ken Kin Lam Yung, Shaogang Qu, Allen Ka Loon Cheung, Stephen Cho Wing Sze
Since the outbreak of COVID-19 has resulted in over 313,000,000 confirmed cases of infection and over 5,500,000 deaths, substantial research work has been conducted to discover agents/ vaccines against COVID-19. Undesired adverse effects were observed in clinical practice and common vaccines do not protect the nasal tissue. An increasing volume of direct evidence based on clinical studies of traditional Chinese medicines (TCM) in the treatment of COVID-19 has been reported. However, the safe anti-inflammatory and anti-fibrotic proprietary Chinese medicines nasal spray, designated as Allergic Rhinitis Nose Drops (ARND), and its potential of re-purposing for suppressing viral infection via SARS-CoV-2 RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding have not been elucidated. To characterize ARND as a potential SARS-CoV-2 entry inhibitor for its possible preventive application in anti-virus hygienic agent. Network pharmacology analysis of ARND was adopted to asacertain gene targets which were commonly affected by COVID-19. The inhibitory effect of ARND on viral infection was determined by an in vitro pseudovirus assay. Furthermore, ARND was confirmed to have a strong binding affinity with ACE2 and SARS-CoV-2 spike-RBD (Delta) by ELISA. Finally, inflammatory and fibrotic cell models were used in conjunction in this study. The results suggested ARND not only inhibited pseudovirus infection and undermined the binding affinity between ACE2 and the Spike protein (Delta), but also attenuated the inflammatory response upon infection and may lead to a better prognosis with a lower risk of pulmonary fibrosis. The data in this study also provide a basis for further development of ARND as an antiviral hygienic product and further investigations on ARND in the live virus, in vivo and COVID-19 patients. ARND holds promise for use in the current COVID-19 outbreak as well as in future pandemics. ARND could be considered as a safe anti-SARS-CoV-2 agent with potential to prevent SARS-CoV-2 coronavirus infection.
Challenges and patenting strategies for Chinese herbal medicineChinese Medicine - Tập 5 - Trang 1-4 - 2010
Xinsheng Wang, Albert Wai-Kit Chan
Patents for Chinese herbal medicines can be difficult to obtain. When the active ingredients of an herbal formula are known, danfang (single herb prescriptions) is better protected with quantified composition claims. When the active ingredients are unknown, 'product by processing', 'method of processing', 'method of administration' and 'new use claims' are often powerful tools to distinguish a traditional danfang from 'the prior art'. Additional patents may also be filed continuously in the product development process. Existing patents for fufang (composite prescriptions) are primarily drafted to protect traditional herbal formulations. More efforts are needed to protect various herbal combinations and their multiple applications.
Efficacy and safety of traditional Chinese medicines for non-alcoholic fatty liver disease: a systematic literature review of randomized controlled trialsChinese Medicine - Tập 16 Số 1
Zhiyao Liang, Xianwen Chen, Junnan Shi, Hao Hu, Yan Xue, Carolina Oi Lam Ung
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease that may progress into, in the absence of proper treatment, severe liver damage. While the optimal pharmacotherapy for NAFLD remains uncertain and the adherence to lifestyle interventions is challenging, the use of herbal medicines such as traditional Chinese medicines (TCMs) to manage the condition is common. The evidence about TCMs in the management of NAFLD is continuously developing through randomized controlled trials (RCTs). This study aims to identify and evaluate the emerging evidence about the efficacy and safety of TCMs for NAFLD.
Methods
A systematic literature search was conducted to identify RCTs which investigated TCMs in the management of NAFLD published in 6 electronic databases including PubMed, the Cochrane Library, EMBASE, Web of Science, Scopus and China National Knowledge Infrastructure since inception to September 2020. RCTs comparing TCMs with no treatment, placebo, non-pharmacological and/or pharmacological interventions were included irrespective of language or blinding. The quality of reporting was evaluated using the Consolidated Standards of Reporting Trials Statement extensions for Chinese herbal medicine Formulas (CONSORT-CHM). Risk-of-bias for each study was assessed using the Cochrane risk of bias tool.
Results
A total of 53 RCTs involving 5997 participants with NAFLD were included in this review. Each included RCT tested a different TCMs giving a total of 53 TCMs identified in this study. Based on the evaluation of the RCT results, TCMs might have various beneficial effects such as improving TCM syndrome score, liver function, and body lipid profile. A range of non-serious, reversible adverse effects associated with the use of TCMs were also reported. However, no conclusion about the efficacy and safety of TCMs in NAFLD can be made. The quality of reporting was generally poor and the risks of bias was mostly uncertain in all trials.
Conclusions
There is some evidence from RCTs that supported the effectiveness and safety of TCMs for NAFLD. However, no conclusive recommendations can be made due to the questionable quality of the RCTs. Improvement in the RCT protocol, the use of a larger sample size, a setting of multicenter, and a more focused approach in selecting TCMs are recommended for developing high quality evidence about the use of TCMs in managing NAFLD.
