Comparative study on registration application of proprietary Chinese medicine in the Guangdong-Hong Kong-Macau Greater Bay Area of China.

Background: Proprietary Chinese medicine (PCM) is widely used in the Guangdong-Hong Kong-Macau Greater Bay Area (GBA) of China. However, the regulatory frameworks and procedures for PCM registration in the region are not well-established, and there are differences among the three jurisdictions. The study is aimed to compare the legal basis, regulatory guidelines, application requirements, and evaluation criteria in each jurisdiction. Methods: We conducted a comprehensive review of the registration application processes for PCMs in the Chinese mainland, Hong Kong, and Macau based on publicly available information from respective regulators. Results: The study found that the registration application process in the GBA was complex and time-consuming, with differences in requirements and procedures among the three jurisdictions. The study also identified several challenges faced by PCM manufacturers, such as the lack of harmonisation of regulatory requirements and procedures and the requirement of package inserts and labelling for PCM products. The study proposed recommendations for improving the registration process and promoting the development of the PCM industry in the GBA. Conclusion: This study provides a comprehensive understanding of the PCM product license application procedures and requirements in the GBA, coupled with discernment of their similarities and disparities, equips applicants with the knowledge to formulate an appropriate strategy for obtaining product approval. Exploring potential methods for harmonising the regulatory process stands to benefit manufacturers, regulators, and patients by improving efficiency and curtailing costs.

Non-drug interventions of traditional Chinese medicine in preventing type 2 diabetes: a review.

Traditional Chinese medicine (TCM) is increasingly used to manage type 2 diabetes and its nonpharmacological interventions are showing potential for preventing type 2 diabetes. This study mainly reviews relevant research. The most mentioned non-drug treatments for preventing type 2 diabetes in TCM are healthy diet, physical activity, emotional therapy, and acupuncture. In most studies, blood glucose status in patients with prediabetes and type 2 diabetes was significantly improved after TCM non-drug interventions, and there was no significant difference between the adverse effect of TCM and control groups or other intervention groups, while the methodological quality of the clinical trials involving TCM generally kept a low level. The effectiveness of TCM in preventing type 2 diabetes has yet to be validated in large randomized controlled trials and the underlying mechanism also needs further exploration.

Quality evaluation methods of chinese medicine based on scientific supervision: recent research progress and prospects.

Traditional Chinese medicine (TCM) is increasingly getting attention worldwide, as it has played a very satisfactory role in treating COVID-19 during these past 3 years, and the Chinese government highly supports the development of TCM. The therapeutical theory and efficacies of Chinese medicine (CM) involve the safety, effectiveness and quality evaluation of CM, which requires a standard sound system. Constructing a scientific and reasonable CM quality and safety evaluation system, and establishing high-quality standards are the key cores to promote the high-quality development of CM. Through the traditional quality control methods of CM, the progress of the Q-marker research and development system proposed in recent years, this paper integrated the research ideas and methods of CM quality control and identified effective quality parameters. In addition, we also applied these effective quality parameters to create a new and supervision model for the quality control of CM. In conclusion, this review summarizes the methods and standards of quality control research used in recent years, and provides references to the quality control of CM and how researchers conduct quality control experiments.

A mannitol-modified emodin nano-drug restores the intestinal barrier function and alleviates inflammation in a mouse model of DSS-induced ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative present in various medicinal herbs, has demonstrated therapeutic effects against UC. However, low bioavailability due to poor water solubility limits its clinical applications. METHODS: Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and they modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal macrophages that express mannose receptors. UC was induced in a mouse model using dextran sulfate sodium (DSS), and different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured using enzyme-linked immunosorbent assay. Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR, and western blotting were performed to assess intestinal barrier dysfunction. RESULTS: Both EmB and EmB-MO markedly alleviated the symptoms of UC, including body weight loss, stool inconsistency, and bloody stools and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger than those of EmB and similar to those of 5-aminosalicylic acid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium and restored the levels of the gut barrier proteins such as ZO-1 and Occludin. CONCLUSIONS: EmB-MO encapsulation significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced UC. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.

Xiaoxuming decoction cutting formula reduces LPS-stimulated inflammation in BV-2 cells by regulating miR-9-5p in microglia exosomes.

The Background: Stroke is one of the leading causes of morbidity and mortality, and the inflammatory mechanism plays a crucial role in stroke-related brain injury and post-ischemic tissue damage. Xiaoxuming decoction (XXMD) is the first prescription for the treatment of "zhongfeng" (a broad concept referring to stroke) in the Tang and Song Dynasties of China and has a significant position in the history of stroke treatment. Through the study of ancient medical records and modern clinical evidence, it is evident that XXMD has significant efficacy in the treatment of stroke and its sequelae, and its pharmacological mechanism may be related to post-stroke inflammation. However, XXMD contains 12 medicinal herbs with complex composition, and therefore, a simplified version of XXMD, called Xiaoxuming decoction cutting (XXMD-C), was derived based on the anti-inflammatory effects of the individual herbs. Therefore, it is necessary to explore and confirm the anti-inflammatory mechanism of XXMD-C. Aim of the study: Based on the previous experiments of our research group, it was found that both XXMD and XXMD-C have anti-inflammatory effects on LPS-induced microglia, and XXMD-C has a better anti-inflammatory effect. Since miRNAs in exosomes also participate in the occurrence and development of cardiovascular diseases, and traditional Chinese medicine can regulate exosomal miRNAs through intervention, this study aims to explore the anti-inflammatory mechanism of XXMD-C in the treatment of post-stroke inflammation through transcriptome sequencing, providing a basis for the application of XXMD-C. Materials and methods: XXMD-C was extracted using water and filtered through a 0.22 µm membrane filter. The main chemical components of the medicinal herbs in XXMD-C were rapidly qualitatively analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Cell viability was determined using the CCK-8 assay, and an LPS-induced BV-2 cell inflammation model was established. The expression of inflammatory cytokines was detected using ELISA and Western blot (WB). Extracellular vesicles were extracted using ultracentrifugation, and identified using transmission electron microscopy (TEM), nanoparticle tracking analysis, and WB. Differential miRNAs were screened using smallRNA-seq sequencing, and validated using RT-PCR and Western blot. Results: The UPLC-Q-TOF-MS analysis revealed that representative components including ephedrine, pseudoephedrine, cinnamaldehyde, baicalin, baicalein, wogonin, and ginsenoside Rg1 were detected in XXMD-C. The results of ELISA and WB assays showed that XXMD-C had a therapeutic effect on LPS-induced inflammation in BV-2 cells. TEM, nanoparticle tracking analysis, and WB results demonstrated the successful extraction of extracellular vesicles using high-speed centrifugation. Differential miRNA analysis by smallRNA-seq identified miR-9-5p, which was validated by RT-PCR and WB. Inhibition of miR-9-5p was found to downregulate the expression of inflammatory factors including IL-1ß, IL-6, iNOS, and TNF-α. Conclusion: The study found that XXMD-C has anti-neuroinflammatory effects. Through smallRNA-seq sequencing of extracellular vesicles, miR-9-5p was identified as a key miRNA in the mechanism of XXMD-C for treating neuroinflammation, and its in vivo anti-inflammatory mechanism deserves further investigation.

Neural oscillations during acupuncture imagery partially parallel that of real needling.

Introduction: Tasks involving mental practice, relying on the cognitive rehearsal of physical motors or other activities, have been reported to have similar patterns of brain activity to overt execution. In this study, we introduced a novel imagination task called, acupuncture imagery and aimed to investigate the neural oscillations during acupuncture imagery. Methods: Healthy volunteers were guided to watch a video of real needling in the left and right KI3 (Taixi point). The subjects were then asked to perform tasks to keep their thoughts in three 1-min states alternately: resting state, needling imagery left KI3, and needling imagery right KI3. Another group experienced real needling in the right KI3. A 31-channel-electroencephalography was synchronously recorded for each subject. Microstate analyses were performed to depict the brain dynamics during these tasks. Results: Compared to the resting state, both acupuncture needling imagination and real needling in KI3 could introduce significant changes in neural dynamic oscillations. Moreover, the parameters involving microstate A of needling imagery in the right KI3 showed similar changes as real needling in the right KI3. Discussion: These results confirm that needling imagination and real needling have similar brain activation patterns. Needling imagery may change brain network activity and play a role in neural regulation. Further studies are needed to explore the effects of acupuncture imagery and the potential application of acupuncture imagery in disease recovery.

Study on basic and clinical application of Shufeng Jiedu Capsule in treating respiratory tract infection.

Shufeng Jiedu Capsule (SFJDC), composed of eight herbs, is a big brand traditional Chinese medicine (TCM) for the treatment of different respiratory tract infectious diseases with good clinical efficacy and few side effects. It is clinically applied to acute upper respiratory tract infection(URI), influenza, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), community-acquired pneumonia(CAP) and other diseases, due to its antibacterial, antiviral, anti-inflammatory, immunoregulatory and antipyretic activities. In particular, it has shown good clinical effects for COVID-19, and was included in the fourth to tenth editions of the 'Diagnosis and Treatment Protocol for COVID-19 (Trial)' by the National Health Commission. In recent years, studies on the secondary development which focus on the basic and clinical application of SFJDC have been widely reported. In this paper, chemical components, pharmacodynamic material basis, mechanisms, compatibility rule and clinical application were systematically summarized, in order to provide theoretical and experimental basis for further research and clinical application of SFJDC.

The safety of Chinese medicine: A systematic review of endogenous substances and exogenous residues.

BACKGROUND: Safety and toxicity have become major challenges in the internationalization of Chinese medicine. Inspite of its wide application, security problems of Chinese medicine still occur from time to time, raising widespread concerns about its safety. Most of the studies either only partially discussed the intrinsic toxicities or extrinsic harmful residues in Chinese medicine, or briefly described detoxification and attenuation methods. It is necessary to systematically discuss Chinese medicine's extrinsic and intrinsic toxic components and corresponding toxicity detoxification or detection methods as a whole. PURPOSE: This review comprehensively summarizes various toxic components in Chinese medicine from intrinsic and extrinsic. Then the corresponding methods for detoxification or detection of toxicity are highlighted. It is expected to provide a reference for safeguards for developing and using Chinese medicine. METHODS: A literature search was conducted in the databases, including PubMed, Web of Science,Wan-fang database, and the China National Knowledge Infrastructure (CNKI). Keywords used were safety, toxicity, intrinsic toxicities, extrinsic harmful residues, alkaloids, terpene and macrolides, saponins, toxic proteins, toxic crystals, minerals, heavy metals, pesticides, mycotoxins, sulfur dioxide, detoxification, detection, processing (Paozhi), compatibility (Peiwu), Chinese medicine, etc., and combinations of these keywords. All selected articles were from 2006 to 2022, and each was assessed critically for our exclusion criteria. Studies describe the classification of toxic components of Chinese medicine, the toxic effects and mechanisms of Chinese medicine, and the corresponding methods for detoxification or detection of toxicity. RESULTS: The toxic components of Chinese medicines can be classified as intrinsic toxicities and extrinsic harmful residues. Firstly, we summarized the intrinsic toxicities of Chinese medicine, the adverse effects and toxicity mechanisms caused by these components. Next, we focused on the detoxification or attenuation methods for intrinsic toxicities of Chinese medicine. The other main part discussed the latest progress in analytical strategies for exogenous hazardous substances, including heavy metals, pesticides, and mycotoxins. Beyond reviewing mainstream instrumental methods, we also introduced the emerging biochip, biosensor and immuno-based techniques. CONCLUSION: In this review, we provide an overall assessment of the recent progress in endogenous toxins and exogenous hazardous substances concerning Chinese medicine, which is expected to render deeper insights into the safety of Chinese medicine.

The effects of bioactive components from the rhizome of gastrodia elata blume (Tianma) on the characteristics of Parkinson's disease.

Parkinson's disease (PD) is an age-related chronic neurodegenerative disease caused by the death and degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The decrease of the neurotransmitter dopamine in the patient's brain leads to various motor symptoms. PD drugs mainly enhance dopamine levels but cannot prevent or slow down the loss of dopaminergic neurons. In addition, they exhibit significant side effects and addiction issues during long-term use. Therefore, it is particularly urgent to develop novel drugs that have fewer side effects, can improve PD symptoms, and prevent the death of dopaminergic neurons. The rhizome of Gastrodia elata Blume (Tianma) is a well-known medicinal herb and has long been used as a treatment of nervous system-related diseases in China. Several clinical studies showed that formula comprising Tianma could be used as an add-on therapy for PD patients. Pharmacological studies indicated that Tianma and its bioactive components can reduce the death of dopaminergic neurons, α-synuclein accumulation, and neuroinflammation in various PD models. In this review, we briefly summarize studies regarding the effects of Tianma and its bioactive components' effects on major PD features and explore the potential use of Tianma components for the treatment of PD.

The Positive and Negative Effects of Calcium Supplementation on Mortality in Septic ICU Patients Depend on Disease Severity: A Retrospective Study from the MIMIC-III.

Background: Calcium administration in septic patients with hypocalcemia is a controversial issue. The present study preliminarily investigated the effects of calcium supplementation on the length of hospitalization and mortality in septic ICU patients with different severities of hypocalcemia and disease. Method: A total of 5761 eligible septic patients, including 2689 who received calcium supplementation and 3072 who did not receive calcium supplementation, were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The cofounding covariates between the calcium supplement and nonsupplement groups were balanced using the propensity score matching model. We compared the length of stay (LOS) in the ICU and hospital with 28-day and hospital mortality and stratified the analysis according to the sequential organ failure assessment (SOFA) score and ionized calcium (iCa) at the first ICU admission in the matched groups. Results: The results showed that iCa at the first ICU admission was associated with mortality in sepsis patients (HR: 0.421; 95% CI: 0.211∼0.837), but the lowest mortality rate was observed in patients with mild hypocalcemia. A total of 993 paired patients were included in the analysis after propensity score matching. Regardless of the SOFA score or presence of iCa, the LOS in the ICU was higher in the calcium supplement group than in the nonsupplement group. The survival analysis was stratified by the SOFA score and showed that calcium supplementation reduced mortality when the patient's SOFA score was ≥8 (p=0.002), and it worsened the outcome when the patient's SOFA score was ≤4 (p=0.010). It had no significant effect on patients with SOFA scores ranging from 5 to 7 (p=0.911). Conclusion: Our results showed that mild hypocalcemia may be protective in septic patients, and calcium supplementation may have positive and negative effects on mortality depending on disease severity. The SOFA score may be a valuable clinical index for decisions regarding calcium administration.

Phytochemistry, Pharmacology and Quality Control of Xiasangju: A Traditional Chinese Medicine Formula.

As a traditional Chinese herbal formula, Xiasangju (XSJ) is widely used in China for antipyresis and influenza treatment. However, XSJ still fails to have a comprehensive summary of the research progress in the last decade. This review summarizes the advanced research on the extraction process, phytochemistry, pharmacological activity, and quality control of XSJ. Current research mainly focuses on quality control and the pharmacological effects of single herbs and active ingredients, but many pharmacological mechanisms of the formula are unclear. The development of active ingredients reflects the active characteristics of triterpenes, phenolic acids and flavonoids, but the hepatotoxicity of Prunella vulgaris L. has not been taken into account. XSJ has extensive historical practical experiences, while systematic clinical trials remain lacking. Therefore, it is necessary to study the active ingredients and define the mechanisms of XSJ to develop multiple applications, and further studies on the dose range between its hepatoprotective activity and hepatotoxicity are necessary to improve the safety of the clinical application. In this review, the current problems are discussed to facilitate the reference basis for the subsequent research on the development of XSJ and future application directions.

Holism of Chinese herbal medicine prescriptions for inflammatory bowel disease: A review based on clinical evidence and experimental research.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic nonspecific inflammatory disease that causes a heavy burden and lacks effective treatments. Chinese herbal medicine prescriptions (CHMPs), which are characterized by a synergistic usage of herbs, are widely used in the management of IBD. The molecular mechanisms of action of CHMP are still ambiguous as the canonical "one-compound-one-target" approach has difficulty describing the dynamic bioreactions among CHMP objects. It seems more flexible to define the holism of CHMP for IBD by employing high-throughput analysis. However, studies that discuss the development of CHMP in treating IBD in a holistic view are still lacking. PURPOSE: This review appraised preclinical and clinical research to fully describe the anti-IBD capacity of CHMPs and discussed CHMPs' holistic characteristics that can contribute to better management of IBD. METHODS & RESULTS: We screened clinical and preclinical references of CHMP being used as treatments for IBD. We discussed the complexity of IBD and the development of CHMP to present the sophistication of CHMP treatments. To describe the clinical effectiveness of CHMPs against IBD, we performed an umbrella review of CHMP-associated META analyses, in which 1174 records were filtered down to 12 references. Then, we discussed 14 kinds of CHMPs that had a long history of use and analyzed their mechanisms of action. Representative herbs were employed to provide a subordinate explanation for the whole prescription. As holism is the dominant characteristic of CHMPs, we explored applications of CHMPs for IBD with the help of omics, gut microbiome, and network pharmacology, which are potential approaches to a dynamic figure of bioactions of CHMPs. CONCLUSION: This review is the first to discuss the potential of CHMPs to manage IBD in a holistic context and will provide inspiring explanations for CHMP applications for further product transformation and application to other diseases.

Screening of the active Ingredients in Huanglian Jiedu decoction through amide bond-Immobilized magnetic nanoparticle-assisted cell membrane chromatography.

Introduction: The Huanglian Jiedu decoction (HLJDD) is a Chinese herbal formula that exerts neuroprotective effects by alleviating oxidative stress injuries and may potentially be prescribed for treating Alzheimer's disease; however, its active ingredients have not yet been identified. Cell membrane chromatography is a high-throughput method for screening active ingredients, but traditional cell membrane chromatography requires multiple centrifugation steps, which affects its separation efficiency. Magnetic nanoparticles are unparalleled in solid-liquid separation and can overcome the shortcomings of traditional cell membrane chromatography. Methods: In this study, the neuroprotective effects of the components of HLJDD were screened through a novel magnetic nanoparticle-assisted cell membrane chromatography method. Magnetic nanoparticles and cell membranes were stably immobilized by amide bonds. Magnetic bead (MB)-immobilized cell membranes of HT-22 cells were incubated with the HLJDD extract to isolate specific binding components. The specific binding components were then identified by ultraperformance liquid chromatography (UPLC)-Orbitrap Fusion Tribrid MS after solid-phase extraction. The bioactivity of these components was analyzed in an HT-22 cellular model of glutamate-induced injury. Results and Discussion: The preparation method of the composite of cell membrane and MBs has the advantages of simple preparation and no introduction of toxic organic reagents. MBs not only provide support for cell membranes, but also greatly improve the separation efficiency compared with traditional cell membrane chromatography. Fifteen of these components were found to specifically bind to the cell membranes, and seven of them were confirmed to reduce varying degrees of glutamate-induced toxicity in HT-22 cells. In conclusion, our findings suggest that the amide bond-based immobilization of magnetic nanoparticles on cell membranes, along with solid-phase extraction and UPLC, is an effective method for isolating and discovering the bioactive components of traditional Chinese medicines.

The Pharmacological Rationales and Molecular Mechanisms of Ganoderma lucidum Polysaccharides for the Therapeutic Applications of Multiple Diseases.

As a versatile Chinese herb, Ganoderma lucidum (Leyss. ex Fr.) Karst (G. lucidum) has been applied to treat multiple diseases in clinics and improve the quality of life of patients. Among all of its extracts, the main bioactive components are G. lucidum polysaccharides (GLPs), which possess many therapeutic effects, such as antitumor, immunoregulatory, anti-oxidant, antidiabetic, antibacterial, and antifungal effects and neuroprotection activities. This review briefly summarized the recent studies of the pharmacological rationales of GLPs and their underlying molecular signaling transmission mechanisms in treating diseases. Until now, the clear mechanisms of GLPs for treating diseases have not been reported. In this review, we used the keywords of "Ganoderma lucidum polysaccharides" and "tumor" to search in PubMed (years of 1992-2020), then screened and obtained 160 targets of antitumor activities in the literatures. The network pharmacology and mechanism framework were employed in this study as powerful approaches to systematically analyze the complicated potential antitumor mechanisms and targets of GLPs in cancer. We then found that there are 69 targets and 21 network pathways in "Pathways in cancer". Besides, we summarized the effects of GLPs and the models and methods used in the research of GLPs. In conclusion, GLPs have been studied extensively, but more in-depth research is still needed to determine the exact mechanisms and pathways. Therefore, this review might provide new insights into the vital targets and pathways for researchers to study the pharmacological mechanisms of GLPs for the treatment of diseases.

Exploring potential mechanisms of Suhexiang Pill against COVID-19 based on network pharmacology and molecular docking.

BACKGROUND: The traditional Chinese medicine prescription Suhexiang Pill (SHXP), a classic prescription for the treatment of plague, has been recommended in the 2019 Guideline for coronavirus disease 2019 (COVID-19) diagnosis and treatment of a severe type of COVID-19. However, the bioactive compounds and underlying mechanisms of SHXP for COVID-19 prevention and treatment have not yet been elucidated. This study investigates the mechanisms of SHXP in the treatment of COVID-19 based on network pharmacology and molecular docking. METHODS: First, the bioactive ingredients and corresponding target genes of the SHXP were screened from the traditional Chinese medicine systems pharmacology database and analysis platform database. Then, we compiled COVID-19 disease targets from the GeneCards gene database and literature search. Subsequently, we constructed the core compound-target network, the protein-protein interaction network of the intersection of compound targets and disease targets, the drug-core compound-hub gene-pathway network, module analysis, and hub gene search by the Cytoscape software. The Metascape database and R language software were applied to analyze gene ontology biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, AutoDock software was used for molecular docking of hub genes and core compounds. RESULTS: A total of 326 compounds, 2450 target genes of SHXP, and 251 genes related to COVID-19 were collected, among which there were 6 hub genes of SHXP associated with the treatment of COVID-19, namely interleukin 6, interleukin 10, vascular endothelial growth factor A, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and epidermal growth factor. Functional enrichment analysis suggested that the effect of SHXP against COVID-19 is mediated by synergistic regulation of several biological signaling pathways, including Janus kinase/ STAT3, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), T cell receptor, TNF, Nuclear factor kappa-B, Toll-like receptor, interleukin 17, Chemokine, and hypoxia-inducible factor 1 signaling pathways. SHXP may play a vital role in the treatment of COVID-19 by suppressing the inflammatory storm, regulating immune function, and resisting viral invasion. Furthermore, the molecular docking results showed an excellent binding affinity between the core compounds and the hub genes. CONCLUSION: This study preliminarily predicted the potential therapeutic targets, signaling pathways, and molecular mechanisms of SHXP in the treatment of severe COVID-19, which include the moderate immune system, relieves the "cytokine storm," and anti-viral entry into cells.

Curcumin prevents As3+-induced carcinogenesis through regulation of GSK3ß/Nrf2.

BACKGROUND: Arsenic (As3+) is a carcinogen with considerable environmental and occupational relevancy. Its mechanism of action and methods of prevention remain to be investigated. Previous studies have demonstrated that ROS is responsible for As3+-induced cell transformation, which is considered as the first stage of As3+ carcinogenesis. The NF-E2 p45-related factor-2 (Nrf2) signaling pathway regulates the cellular antioxidant response, and activation of Nrf2 has recently been shown to limit oxidative damage following exposure to As3+ METHODS AND RESULTS: In this study, molecular docking was used to virtually screen natural antioxidant chemical databases and identify molecules that interact with the ligand-binding site of Keap1 (PDB code 4L7B). The cell-based assays and molecular docking findings revealed that curcumin has the best inhibitory activity against Keap1-4L7B. Co-immunoprecipitation (Co-IP) results indicated that curcumin is a potent Keap1 Kelch domain-dependent Nrf2 activator that stabilizes Nrf2 by hindering its ubiquitination. The increased activation of Nrf2 and its target antioxidant genes by curcumin could significantly decrease As3+-generated ROS. Moreover, curcumin induced autophagy in As3+-treated BEAS-2B via inducing autophagy by the formation of a p62/LC-3 complex and increasing autophagic flux by promoting transcription factor EB (TFEB) and lysosome-associated membrane protein 1 (LAMP1) expression. Knockdown of Nrf2 abolished curcumin-induced autophagy and downregulated ROS. Further studies showed that inhibition of autophagosome and lysosome fusion with bafilomycin a1 (BafA1) could block curcumin and prevented As3+-induced cell transformation. These results demonstrated that curcumin prevents As3+-induced cell transformation by inducing autophagy via the activation of the Nrf2 signaling pathway in BEAS-2B cells. However, overexpression of Keap-1 showed a constitutively high level of Nrf2 in As3+-transformed BEAS-2B cells (AsT) is Keap1-independent regulation. Overexpression of Nrf2 in AsT demonstrated that curcumin increased ROS levels and induced cell apoptosis via the downregulation of Nrf2. Further studies showed that curcumin decreased the Nrf2 level in AsT by activating GSK-3ß to inhibit the activation of PI3K/AKT. Co-IP assay results showed that curcumin promoted the interaction of Nrf2 with the GSK-3ß/ß-TrCP axis and ubiquitin. Moreover, the inhibition of GSK-3ß reversed Nrf2 expression in curcumin-treated AsT, indicating that the decrease in Nrf2 is due to activation of the GSK-3ß/ß-TrCP ubiquitination pathway. Furthermore, in vitro and in vivo results showed that curcumin induced cell apoptosis, and had anti-angiogenesis and anti-tumorigenesis effects as a result of activating the GSK-3ß/ß-TrCP ubiquitination pathway and subsequent decrease in Nrf2. CONCLUSIONS: Taken together, in the first stage, curcumin activated Nrf2, decreased ROS, and induced autophagy in normal cells to prevent As3+-induced cell transformation. In the second stage, curcumin promoted ROS and apoptosis and inhibited angiogenesis via inhibition of constitutive expression of Nrf2 in AsT to prevent tumorigenesis. Our results suggest that antioxidant natural compounds such as curcumin can be evaluated as potential candidates for complementary therapies in the treatment of As3+-induced carcinogenesis.

A recent update on the use of Chinese medicine in the treatment of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic idiopathic disease that is characterized by inflammation of the gastrointestinal tract. Proper management of IBD requires both early diagnosis and novel therapies and management programs. Many reports have suggested that Chinese medicine has unique properties favorable to the treatment of IBD. However, there are no systematic analyses on this topic. PURPOSE: This review summarizes recent studies that assessed the effects and mechanisms of Chinese medicine in the treatment of IBD in order to fully understand the advantages of Chinese medicine in the management of IBD. METHODS: A literature search was conducted using peer-reviewed and clinical databases, including PubMed, Web of Science, ClinicalTrials.gov, MEDLINE, EMBASE, Springer LINK, Wan-fang database, the Chinese Biomedicine Database, and the China National Knowledge Infrastructure (CNKI). Keywords used were inflammatory bowel disease (including Ulcerative colitis or Crohn's disease) and Chinese medicine. All selected articles were from 1997 to 2021, and each were assessed critically for our exclusion criteria. Studies describing the pathogenesis of IBD, the effects and mechanisms of Chinese medicine in the treatment of IBD, in particular their roles in immune regulation, intestinal flora regulation, and improvement of intestinal barrier function, were included. CONCLUSION: This review highlights recent progress in the use of Chinese medicine in the treatment of IBD. It also provides a reference for further evaluation and exploration of the potential of classical multi-herbal Chinese medicine in the treatment of IBD.

The key issues and development strategy of Chinese Classical Formulas pharmaceutical preparations.

It is well-known that Prof. Tu Youyou won the Nobel Prize in Physiology or Medicine in 2015 due to the research on artemisinin treating malaria, and this can be regarded as the milestone of modernization of Traditional medicine. This first Nobel Prize in Traditional Chinese medicine (TCM) has aroused profound impetus in the investigation of TCM and attracted global attention to the ancient books of TCM. Three new medicines for the treatment of COVID-19 derived from Chinese Classical Formula (, CCF) have been approved in 2021 due to their effectiveness for the treatment of COVID-19. This article introduced the research background of CCF pharmaceutical preparation (CCFPP), explained the ideas for the modernization of CCF and analyzed related issues involved in the development process of CCFPP, including the origin of medicinal materials, processing methods, dosages and the preparation process of CCF Material Reference. The strategy for industrialization was proposed in terms of the evaluation of the pharmaceutical properties, industrialization considerations, and clinical positioning of CCFPP. The key contents and requirements for the development CCFPP were also summarized according to the recently published registration guidance by the Center for Drug Evaluation in China. In addition, the safety issues of CCFPP were described, including the discussion on the non-clinical safety evaluation and analyzation on the international registration of Traditional herbal medicines. This article is aimed to provide references for enterprises, researchers, and relevant personnel of government departments that are engaged in the development of CCF to speed up the developing process of CCFPP.

Panax notoginseng Saponins Modulate the Inflammatory Response and Improve IBD-Like Symptoms via TLR/NF-[Formula: see text]B and MAPK Signaling Pathways.

Panax notoginseng saponins (PNS) are the main active ingredients of Panax notoginseng (Burk) F. H. Chen, which are used as traditional Chinese medicine for thousands of years and have various clinical effects, including anti-inflammation, anti-oxidation, and cardiovascular protection. Inflammatory bowel disease (IBD) is a complex gastrointestinal inflammatory disease that cannot be cured completely nowadays. The anti-inflammatory and protective effects of PNS were analyzed in vitro and in dextran sulfate sodium (DSS)-induced colitis mouse model. PNS inhibited the release of nitric oxide (NO), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text], interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in Pam3CSK4-induced RAW 264.7 macrophages. In the animal study, compared with DSS-induced mice, PNS reduced the expression of pro-inflammatory cytokines (TNF-[Formula: see text], IL-6, and MCP-1) in the colon tissues. Furthermore, PNS treatment led to a remarkable reduction in the activation of the inhibitor of nuclear factor kappa-B kinase [Formula: see text]/[Formula: see text] (IKK[Formula: see text]/[Formula: see text], I[Formula: see text]B[Formula: see text] and p65 induced by DSS. On the other hand, PNS inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase 1/2 (ERK1/2). Taken together, our results suggested that PNS conferred profound protection for colitis mice through the downregulation of mitogen-activated protein kinase (MAPK) and NF-[Formula: see text]B signaling pathways, which were associated with reducing inflammatory responses, alleviating tissue damage, and maintaining of intestinal integrity and functionality.

Dissecting the novel mechanism of reduning injection in treating Coronavirus Disease 2019 (COVID-19) based on network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Reduning injection (RDNI) is a patented Traditional Chinese medicine that contains three Chinese herbal medicines, respectively are the dry aboveground part of Artemisia annua L., the flower of Lonicera japonica Thunb., and the fruit Gardenia jasminoides J.Ellis. RDNI has been recommended for treating Coronavirus Disease 2019 (COVID-19) in the "New Coronavirus Pneumonia Diagnosis and Treatment Plan". AIM OF THE STUDY: To elucidate and verify the underlying mechanisms of RDNI for the treatment of COVID-19. METHODS: This study firstly performed anti-SARS-CoV-2 experiments in Vero E6 cells. Then, network pharmacology combined with molecular docking was adopted to explore the potential mechanisms of RDNI in the treatment for COVID-19. After that, western blot and a cytokine chip were used to validate the predictive results. RESULTS: We concluded that half toxic concentration of drug CC50 (dilution ratio) = 1:1280, CC50 = 2.031 mg crude drugs/mL (0.047 mg solid content/mL) and half effective concentration of drug (EC50) (diluted multiples) = 1:25140.3, EC50 = 103.420 µg crude drugs/mL (2.405 µg solid content/mL). We found that RDNI can mainly regulate targets like carbonic anhydrases (CAs), matrix metallopeptidases (MMPs) and pathways like PI3K/AKT, MAPK, Forkhead box O s and T cell receptor signaling pathways to reduce lung damage. We verified that RDNI could effectively inhibit the overexpression of MAPKs, PKC and p65 nuclear factor-κB. The injection could also affect cytokine levels, reduce inflammation and display antipyretic activity. CONCLUSION: RDNI can regulate ACE2, Mpro and PLP in COVID-19. The underlying mechanisms of RDNI in the treatment for COVID-19 may be related to the modulation of the cytokine levels and inflammation and its antipyretic activity by regulating the expression of MAPKs, PKC and p65 nuclear factor NF-κB.