TCM Drugs Research Articles

Effect of Juanbi Qianggu Formula on biological behaviors of fibroblast-like synoviocytes in rheumatoid arthritis by regulating FGFR1 signaling pathway based on network pharmacology and cell function experiments

This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.

Research progress on the treatment of epilepsy with traditional Chinese medicine

BackgroundTraditional Chinese Medicine (TCM) system is a medical system that has been expanding for thousands of years that was formed by the extensive clinical practice experience of many physicians and the accumulation of personal medication habits in China. In TCM, there is a history of long-term medication for epilepsy, the main treatment for epilepsy is TCM drugs and its prescription, supplemented by TCM modalities such as acupuncture therapy, moxibustion therapy, tuina, emotion adjustment therapy, etc. PurposeWith the modernization of TCM, the active ingredients and molecular mechanisms of TCM for epilepsy treatment have been gradually revealed. This review aimed to comprehensively summarize the TCM treatment of epilepsy, focusing on the current TCM drugs and some TCM formulae for the treatment of epilepsy, and to discuss the research progress of TCM for the treatment of epilepsy, and to provide a reference to develop future related studies in this field. Materials and methodsThe mechanism of action of antiepileptic drugs (AEDs) was interpreted from different perspectives by searching online databases and querying various materials identify drugs used in both modern medicine and TCM systems for the treatment of epilepsy. We collected all relevant TCM for epilepsy literature published in the last 30 years up to December 2022 from electronic databases such as PubMed, CNKI and Web of Science, and statistically analyzed the literature for the following keyword information. The search terms comprise the keywords “TCM”, “phytochemistry”, “pharmacological activity”, “epilepsy” and “traditional application” as a combination. Scientific plant names were provided by “The Plant List” (www.theplantlist.org). ResultsEpilepsy is a complex and serious disease of the brain and nervous system. At present, the treatment of epilepsy in modern medicine is mainly surgery and chemotherapy, but there are many serious side effects. By summarizing the treatment of epilepsy in TCM, it is found that there are various methods to treat epilepsy in TCM, mainly TCM drugs and its formulae. Many TCM drugs have antiepileptic effects. Now found that the main effective TCM drugs for the treatment of epilepsy are Curcumae Longae Rhizoma, Scorpio, Acori Tatarinowii Rhizoma, Uncariae Ramulus Cum Uncis and Ganoderma, etc. And the main compounds that play a role in the treatment of epilepsy are curcumin, gastrodin, ligustrazine, baicalin and rhynchophylline, etc. These TCM drugs have played an important role in the treatment of epilepsy in TCM clinic. However, the chemically active components of these TCM drugs are diverse and their mechanisms of action are complex, which are not fully understood and need to be further explored. ConclusionsTCM treats epilepsy in a variety of ways, and with the discovery of a variety of potential bioactive substances for treatment of epilepsy. With the new progress in the research of other TCM treatment methods for epilepsy, TCM will have greater potential in the clinical application of epilepsy.

The Clinical Efficacy and Safety of 11 Commonly Used Treatment Strategies Improving Arrhythmia of CHD in China: A Network Meta-Analysis

Purpose: Arrhythmia which as a common complication of CHD, has a high incidence. At present, more and more anti-arrhythmic drugs are used in clinical practice. However, which drug has the best efficacy and high safety is still unknown. Therefore, we decided to use NMA to solve this problem.Method: We searched CNKI, Wanfang database, VIP database, Pubmed, Embase and Cochrane libraries, and collected all RCTs of arrhythmia of CHD, and used RevMan (5.3) and Stata (13.0) to carry out this NMA. The primary outcome indicator of this study is efficiency; the secondary outcome indicator is the incidence of adverse reactions.Result: A total of 134 RCTs, 13,951 patients, and 11 treatment strategies were included in this NMA. The results show that all treatment strategies can effectively improve the arrhythmia of patients. Among them, PMA+AM, AM+AT, AM+WG have higher effective rates, and PMA+AM, WG+ME, SC+ME have better safety. The effectiveness and safety of the treatment strategies which combined TCM and chemical drugs, are significantly better than that of using chemical drugs alone.Conclusion: The treatment strategy of combination of multiple drugs usually has higher efficiency and safety. PMA+AM seems to be the most recommended treatment strategy. In addition, the rational combination of TCM and chemical drugs may provide potential benefit.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021229693.

Effect of otopoint pellet-pressing combined with medication on clinical symptoms of migraine patients and changes of plasma 5-HT and CGRP contents

To investigate the short-term and long-term clinical effects of otopoint pellet-pressing combined with medication in the treatment of patients with migraine without aura and its impact on plasma 5-hydroxytryptamine(5-HT) and calcitonin gene-related peptide(CGRP) contents. Patients with migraine without aura were randomly divided into medication(control) group(n=48) and otopoint pellet-pressing plus medication (treatment) group(n=49). Patients of the control group were given oral Flunarizine capsules(10 mg/time) twice a day, and those of the treatment group received same dosage of Flunarizine and pellet-pressing of otopoints Nao(Brain), Nie (Temporal), Shenmen(Shenmen), Jiaogan(Sympathy) and Pizhixia(Subcortex), 2 min/point, 3 times a day, simultaneously. The treatment was conducted for 1 month. The short-term and long-term clinical effects were evaluated according to Yang and colleagues' methods, and "Guiding principles for clinical research of new TCM drugs (trial)". The contents of plasma 5-HT and CGRP were detected by ELISA. After one month's treatment, of the 48 and 49 patients in the control and treatment groups, 10(20.83%)and 17(34.69%) were under control, 19(39.59%)and 23(46.94%) experienced marked improvement, 10(20.83%)and 7(14.29%)were effective, 9(18.75%) and 2(4.08%) failed, with the total effective rates being 81.25% and 95.92%, respectively. Six months' follow-up survey showed that of the 48 and 49 patients in the control and treatment groups, 4(8.33%)and 11(22.45%) were under control, 20(41.67%)and 24(48.98%)experienced marked improvement, 11(22.92%)and 9(18.37%)were effective, and 13(27.08%) and 5(10.20%)failed, with the total effective rates being 72.92% and 89.80%, respectively. The number of headache attacks, duration of each attack and the degree of headache were significantly decreased after 1 and 6 months' treatment in both groups in comparison with their own pre-treatment (P<0.05). The contents of plasma 5-HT at the time-points of 1 and 6 months were markedly increased (P<0.05), and those of plasma CGRP at the two time points markedly decreased in both groups in comparison with their own pre-treatment (P<0.05). The therapeutic effects of the treatment group were obviously superior to those of the control group in lowering the number of headache attacks, duration of each attack and the degree of headache and plasma CGRP content, as well as in increasing plasma 5-HT levels after 1 and 6 months' treatment (P<0.05). Otopoint pellet-pressing combined with oral administration of Flunarizine can significantly improve the clinical symptoms in patients with migraine without aura, and possess a stable long-term clinical effect, which may be associated with its effect in increasing plasma 5-HT and decreasing CGRP levels.

Impact analysis of medicine markups abolition on revenue structure of 12 public hospitals in Qingdao

Objective To learn the impact of abolishing medicine markups on the revenue structure of public hospitals in Qingdao city. Methods The business performance of 12 public hospitals directly under the Qingdao Health and Family Planning Commission was analyzed to compare their revenue structure the year before (July 2015 to June 2016) and the year since the reform (July 2016 to June 2017). Results The reform has witnessed increased government subsidies, and decreased revenue from drugs and healthcare materials. For example, the proportion of drug expenditure decreased from 44.21% to 32.71%, while the proportion of medical service income and that of examination and laboratory examination increased to some extent. Conclusions Given the initial success of the reform, challenges remain in further curbing revenues from examinations and checkups, and growing revenue from TCM drugs as well. Key words: Hospitals, public; Medicine markups; Zero margin; Revenue structure; Compensation mechanism

Promoting Chinese Herbal Drugs through Regulatory Globalisation

This study explores the social dynamics in promoting traditional Chinese medicine (tcm) drugs by making them acceptable to biomedical markets. It investigates the Consortium for Globalization of Chinese Medicine (cgcm), an organisation based in Hong Kong in pursuit of advancing tcm, and traces the development of the herbal formula phy906, a Chinese herbal product intensively discussed at the cgcm that has been tested according to the us Food and Drug Administration’s regulation for approval. Departing from accounts on the organisation’s success that focus either on its scientific approach or its leader Yung-chi Cheng, this paper argues that it was the synergy between the cgcm and the pursuit of approval for phy906 that contributed to the regulatory globalisation of tcm. In this process, not only organisations like the cgcm are required to streamline efforts for producing globalised tcm; also researchers are needed who, with cultural commitment, seek for transforming tcm to meet biomedical indications.

Abstract 5339: Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo

Abstract Traditional Chinese medicine (TCM) has held, and still holds, an important position in primary health care in China, especially in the rural areas. However, scientific evidence of its mechanism is, for the most part, limited and additional better-designed laboratory research is needed. To date, numerous leading chemical compounds from TCM drugs have been identified and evaluated for their anti-tumor effects. However, little effort has been made on the protein-encoding genes isolated from TCM drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated viral (rAAV) vectors has not been attempted. For example, Trichosanthin (TCS), an antiviral plant defense protein found in the root tuber of a TCM herb, Trichosanthes kirilowii, has been used in anti-HIV clinical trials in the USA. Its enzymatic activities were recognized as type I ribosome-inactivating protein. Although the nucleotide sequence of the TCS gene was determined more than 20 years ago, to date, there was little report to deliver TCS-encoding gene into malignant cells. In the present studies, we synthesized the cDNAs of five known cytotoxic proteins isolated from TCM drugs and the FLAG epitope-tagged cDNAs were subcloned into a rAAV plasmid vector. The expression of mRNA was confirmed by RT-PCR and protein expression by Western blot assays against the FLAG tag, respectively. Among these genes, TCS gene yielded the most promising results for the inhibition of cancer cell growth in vitro. The over-expressed TCS functioned as a type I ribosome inactivating protein, followed by inducing apoptosis that is associated with the Bcl-PARP signaling pathway. Next, rAAV vectors containing the TCS gene driven by a liver cancer specific promoter, α-fetoprotein promoter (AFPp) were generated and tested. The results indicated that rAAV-AFPp-TCS vectors significantly inhibited the growth of hHCC cell lines in vitro as well as hHCC tumor growth in vivo following intra-tumor injections in a murine xenograft model. These studies suggest that the use of TCM cytotoxic genes may prove to be a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular. Note: This abstract was not presented at the meeting. Citation Format: Yuanhui Zhang, Yuan Wang, Lina Wang, George Aslanidi, Arun Srivastava, Changquan Ling, Chen Ling. Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5339. doi:10.1158/1538-7445.AM2015-5339

Pharmacovigilance practice and risk control of Traditional Chinese Medicine drugs in China: Current status and future perspective

Ethnopharmacological relevanceTraditional Chinese Medicine (TCM), including Traditional Chinese Medicine drugs (TCM drugs), has been playing a very important role in health protection and disease control for thousands of years in China. Relying on natural products, mainly of herbal origin, used either as raw materials for decoction, as prepared herbal medicines or as formulated traditional medicines, TCM is still widely accepted by Chinese people, especially for chronic diseases treatment. This extensive use warrants safety measures and so TCM drug safety monitoring and risk management are becoming increasingly important tasks for the Chinese State Food and Drug Administration (SFDA). MethodsThe Adverse Drug Reaction (ADR) monitoring system in China was established both for western and TCM drugs in 1989 as a voluntary reporting system with a National Center collecting and compiling reports. Serious or multi-case reports on individual TCM drug or formulated products are detailed in the Chinese ADR Information Bulletin to inform the public and Drug Administrative authorities for risk management. ResultsAbout 10–15% of the ADR reports received by the National Center are related to TCM drugs and mainly pertaining to the formulated products. In certain cases, the suspension of a particular TCM preparation is decided by SFDA China. ConclusionThe model of safety monitoring and risk management of TCM drugs is still under exploration. Indeed, the characteristics and risk factors associated with these drugs require both proper understanding and control of the risk by strengthening standardization of clinical applications, basic science research, quality control in manufacturing, exploration of the actives monitoring methodology and enhancement of international communication and cooperation.

Discovery of GABAAReceptor Modulator Aristolactone in a Commercial Sample of the Chinese Herbal Drug “Chaihu” (Bupleurum chinenseRoots) Unravels Adulteration by NephrotoxicAristolochia manshuriensisRoots

In a two-microelectrode voltage clamp assay using Xenopus laevis oocytes, a petroleum ether extract prepared from a commercial sample of the traditional Chinese herbal drug labelled as " Chaihu" (Bupleurum chinense DC. roots) enhanced the I(GABA) by 156 % ± 22 % when tested at 100 µg/mL. By means of HPLC-based activity profiling combined with high-resolution LC-MS and microprobe NMR, the germacranolide aristolactone was identified as one of the main active compounds (EC₅₀ 56.02 µM ± 5.09 µM). However, aristolactone has been previously reported only from the genus Aristolochia (Aristolochiaceae), suggesting a possible adulteration. With the aid of a validated HPTLC protocol for detection of aristolochic acids and with reference samples, the commercial sample was confirmed to be a mixture of Aristolochia manshuriensis root and Bupleurum chinense root. This finding was corroborated by macroscopic inspection of the drug. This case of adulteration with a highly nephrotoxic drug raises concerns about adequate quality control of TCM drugs commercialized in Europe.

New cerebrosides and hydroxylated fatty acids from TCM drugs

New cerebrosides and hydroxylated fatty acids from TCM drugs

Standardized evaluation of TCM drug safety and its safe use in China

Regulatory documents on requirements for TCM drug registration are officially issued, which are divided into 4 levels: Act, Rules, Regulation and Guidance. With the above-mentioned regulations, two-phase and two-level evaluation for TCM drug registration for marketing is established. The requirements for R&D and production of TCM drugs are standardized based on internationally acceptable standards, such as GLP, GCP, GMP and so on. In order to apply for the registration, 4 parts of dossiers should be submitted to SFDA (State Food & Drug Administration in China): Part I: Description and review on the TCM drug; Part II: CMC data; Part III: Pharmacology and toxicology data; and Part IV: Clinical study data. The requirements for TCM are different from Western medicine. And the requirements differ with different category’s TCM drug. Finally, progress in post-market surveillance of adverse reactions of TCM drugs in China is briefly discussed.

S111- a post absorption/metabolism TCM drug, its anti-depression effect and a transcriptomic study

Many chemical ingredients of TCM drugs are poorly absorbed and therefore do not represent the pharmacological mechanisms of the drug. We proposed that one of better approaches to modernize TCM is to study compounds post absorption and metabolism. Compounds found in the blood or target organs after taking TCM drug can be re-synthesized and combined to form a class of novel drugs namely Post Absorption/Metabolism Drugs (PAMDs). Ginseng has been used as a major ingredient in TCM for treatment of depression for many years in China. In the present study, we tested anti-depression effect of a semi-synthesized aglycone ginsenoside S111 that represents one of the post metabolism compounds of ginseng in a series of depression models. Transcriptomics of various brain regions were analysed and compared with that of untreated and fluoxetine, treated animals. Our results showed that orally given S111 daily for consecutive 10 days significantly antagonized Reserpine induced various locomotor inhibition in mice. Animals with given S111 daily, demonstrated substantial improvement in an open-field test. Furthermore, S111 inhibited 5-HT and NE uptake in the brain in acute tests. However, unlike fluoxetine, S111 does not alter concentrations of those neurotransmitters in the brain, suggesting its anti-depressant effect may be mediated by a different mechanism. Further study showed two gene expression profiles between S111 and fluoxetine, indicating that the two drugs may have quite different anti-depression mechanisms. S111 caused much less disturbance in the normal animals than that of fluoxetine and S111 had a better therapeutic efficiency. However, some genes were commonly regulated by both S111 and fluoxetine, suggesting that those genes may represent a group of targets that are critical for anti-depression. Our results are the first to show that a metabolic product of ginseng can be extremely active and perform better therapeutic functions of ginseng. We also demonstrated that approach of system biology can be used to analyze the complicated biological effects of TCM drugs.

New approach for TCM quality control in China

Chinese Pharmacopeia (CP) is the highest legal documented drug standards in China. The development of methodology in CP is aimed at increasing and consummating TCM safety testing methods and establishes scientific and reasonable quality control (QC) for the drugs. Due to the complexity of TCM drugs, methods needs to be continuously improved by the scientific research and then adopted tangible methods in the CP new editions. CP has a new edition every 5 years. The forthcoming edition is on 2010 and is currently under compilation. The new edition focuses on the establishment of specific testing methods which are directly correlated to the quality and can control the quality effectively, and establishment of a new QC pattern conforming to TCM feature-transit from the single component analysis model to the active component analysis plus bioassay model, and then to the multiple component quantitative analysis combined with fingerprint or characteristic print. The current status of Chinese Pharmacopeia was reviewed and various aspects concerned were summarized. The current determination techniques including GC-MS, GC-MS(n), HPLC- MS(n), GC-NPD, GC-ECD ,GC-FPD, HPLC (with Post Column System, Fluoresense Detector) etc. were commented. The current determining capabilities in pesticide residues including instruments, technique, analysis and determination level etc. have reached the top international standards. Over 700 pesticide residues can be determined and determination of common pesticide residues in single sample takes not more than 2 hr. A revision plan has been launched to increase the determining categories of pesticide residues, according to the fact of Chinese fertilization and referring to the international standards and also to increase the number of TCMs for the control of pesticide residues. Over 60 new species, mainly including commonly used, forbidden ones, virulent and difficultly degradated but easily resided in soil and water were planned to be determined. Heavy metals and harmful elements were also in the plan. This presentation gave a complete summary on the current status and future perspective of Chinese Pharmacopeia.

Effects of Siqi Decoction on Concentration of Nitric Oxide and Activity of Nitric Oxide Synthase in Blood Serum of Rats with Myocardial Ischemia

To study the effects of Siqi decoction on rats with Myocardial Ischemia, the model of Myocardium Ischemia was made for the Wistar rats cured with posterior pituitary injection through vein in tail. Siqi decoction, Diaoxinxuekang(DK) and Fufangdanshenpian(FD), the latter two drugs of which were effective TCM drugs of anti-Myocardial Ischemia at present, were administrated to the rats with Myocardium Ischemia for 5 days to compare the effect of anti-Myocardium Ischemia as reference drugs by measuring the changes of NO concentration and activity of NOS in the rat blood serum with Myocardial Ischemia. There was a remarkable increase in the NO concentration and activity of NOS in serum in Siqi decoction groups compared with those in control group(p<0.05). The results of the prevention group in experiment of Siqi decoction are better than those of the cure group. Siqi decoction was really fit for Myocardium Ischemia via increasing NO concentration by stimulating the activity of NOS in serum. The effect of Siqi decoction against Myocardium Ischemia in preventive group is better than the curative that of Siqi decoction in the curative group.

Clinical study on treatment of Alzheimer’s disease from the viewpoint of Xin and Shen

To explore the therapeutic mechanism of Tiaoxin Recipe (TXR) and Bushen Recipe (BSR) in treating Alzheimer's disease (AD). Sixty patients with AD were divided into 3 groups according to their MMSE and ADL scores before treatment, using randomized block design. They were treated separately with TXR, BSR and Donepezil (Dp) for 12 weeks. The changes of MMSE score, ADL score, neuro-psychology amount table score, including FOM, RVR, DS and BD, as well as the overall operational evaluation before and after treatment were analyzed. The recognition and daily life capacity of patients in the 3 groups were improved after treatment. MMSE score in the TXR group increased from 16.10 +/- 1.94 scores before treatment to 17.90 +/- 2.59 scores after treatment, in the BSR group, from 16.15 +/- 2.16 to 17.50 +/- 2.59, and in the Dp group, from 17.35 +/- 1.90 to 19.60 +/- 3.39, all showed significant difference (all P < 0.01). Change of ADL score showed that in TXR from 43.10 +/- 3.86 to 41.50 +/- 4.40, in the BSR group from 43.30 +/- 4.53 to 41.60 +/- 4.12 and in the Dp group, from 42.95 +/- 3.58 to 40.60 +/- 5.23, which also showed significant difference (P < 0.05 or P < 0.01). Moreover, increase of FOM, RVR and DS score was shown in the TXR and the Dp group, and increase of RVR and BD score was shown in the BSR group with significant difference in comparison of corresponding score before and after treatment, inter-groups comparison showed significant difference of FOM score between the BSR and the Dp group (P < 0.01). Overall operational evaluation (total effective rate) in the TXR group was 70%, in the BSR group 65% and in Dp group 75%, with no significant difference among them. TXR and BSR are effective TCM drugs in treating AD.

Alternative Medicine

New Method of Analyzing Chemicals in TCM drugs. China's TCM Producers Urged to Collaborate with Foreign Counterparts.