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Abstract Background Traditional Chinese Medicinal Plants (CMPs) hold a significant and core status for the healthcare system and cultural heritage in China. It has been practiced and refined with a history of exceeding thousands of years for health-protective affection and clinical treatment in China. It plays an indispensable role in the traditional health landscape and modern medical care. It is important to accurately identify CMPs for avoiding the affected clinical safety and medication efficacy by the different processed conditions and cultivation environment confusion. Results In this study, we utilize a self-developed device to obtain high-resolution data. Furthermore, we constructed a visual multi-varieties CMPs image dataset. Firstly, a random local data enhancement preprocessing method is proposed to enrich the feature representation for imbalanced data by random cropping and random shadowing. Then, a novel hybrid supervised pre-training network is proposed to expand the integration of global features within Masked Autoencoders (MAE) by incorporating a parallel classification branch. It can effectively enhance the feature capture capabilities by integrating global features and local details. Besides, the newly designed losses are proposed to strengthen the training efficiency and improve the learning capacity, based on reconstruction loss and classification loss. Conclusions Extensive experiments are performed on our dataset as well as the public dataset. Experimental results demonstrate that our method achieves the best performance among the state-of-the-art methods, highlighting the advantages of efficient implementation of plant technology and having good prospects for real-world applications.

This paper intended to study the mechanism and active ingredients of ACB anti-epilepsy. The antiepileptic activity of ACB validated in PTZ kindled rats, ACB could increase the seizure latency and reduce seizure duration, attenuate spatial learning and memory deficits, improve hippocampus neuronal damage and regulate unbalanced neurotransmitters. Furthermore, network pharmacology and molecular docking analysis predicted four potential active compounds, in addition, PI3K/Akt signal pathway may be the main signal pathway of ACB anti-epilepsy. In vitro, ACB greatly increased the vitality and reduced apoptosis of PC12 cells exposed to H2O2. Additionally, ACB elevated Bcl-2 and downregulated C-caspase-3 and Bax proteins expression. Importantly, ACB improved the phosphorylation of PI3K and Akt in H2O2-stimulated PC12 cells, and stimulated the nuclear transfer of Nrf2. These findings indicated that ACB has effective on antiepileptic by activating of the PI3K/Akt/Nrf2 pathway to reduce oxidative stress and neuronal cell apoptosis.

Abstract The metastasis of non-small cell lung cancer (NSCLC) is the leading death cause of NSCLC patients, which requires new biomarkers for precise diagnosis and treatment. Circular RNAs (circRNAs), the novel noncoding RNA, participate in the progression of various cancers as microRNA or protein sponges. We revealed the mechanism by which circEPB41L2 (hsa_circ_0077837) blocks the aerobic glycolysis, progression and metastasis of NSCLC through modulating protein metabolism of PTBP1 by the E3 ubiquitin ligase TRIP12. With ribosomal RNA-depleted RNA seq, 57 upregulated and 327 downregulated circRNAs were identified in LUAD tissues. circEPB41L2 was selected due to its dramatically reduced levels in NSCLC tissues and NSCLC cells. Interestingly, circEPB41L2 blocked glucose uptake, lactate production, NSCLC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, acting as a scaffold, circEPB41L2 bound to the RRM1 domain of the PTBP1 and the E3 ubiquitin ligase TRIP12 to promote TRIP12-mediated PTBP1 polyubiquitylation and degradation, which could be reversed by the HECT domain mutation of TRIP12 and circEPB41L2 depletion. As a result, circEPB41L2-induced PTBP1 inhibition led to PTBP1-induced PKM2 and Vimentin activation but PKM1 and E-cadherin inactivation. These findings highlight the circEPB41L2-dependent mechanism that modulates the “Warburg Effect” and EMT to inhibit NSCLC development and metastasis, offering an inhibitory target for NSCLC treatment.

The bubbles have been widely applied in industrial processing, including steelmaking. Recently, industrial trials of natively generated bubbles via decomposition reactions have been successfully adopted in steel refining and inclusion removal. The refining efficiency was proved to be outstanding due to the small bubble sizes and the subsequent satisfying dynamic conditions. However, the bubble behaviors, including growth and detachment, are still not thoroughly clarified due to the strict requirements for observation conditions. Therefore, the growth and detachment behavior of the bubbles generated by decomposition reactions were carefully observed with physical modeling and shadow imaging method. The detachment sizes of the bubbles were extracted accordingly. Based on the statistical data on the detachment bubble sizes, a traditional nozzle flow model was modified for the prediction of the bubble detachment size in decomposition reactions. This work provides the foundation for further studies on the interaction mechanism between the natively generated bubbles and the impurities in liquid steel in terms of inclusion removal.

Neurodegenerative diseases are neurological diseases that are characterized by neuronal degeneration and apoptosis; they threaten populations around the world and place a great burden on the social economy. Unfortunately, the drugs currently used to treat neurodegenerative diseases have obvious side effects, making them much less effective. Therefore, discovery of new safe and effective drugs is urgently needed. Zanthoxylum bungeanum Maxim. (ZBM) has a long medicinal history in China and can also be used as food. ZBM contains many types of chemical components, of which amides are the most abundant. In preparing this review, we searched and integrated the relevant literature in PubMed, Web of Science, Elesvier, Wliey and Springer using the keywords “ZBM”, “amide”, “physicochemical properties”, and “neurodegenerative diseases”. It was found that the amides that are present in ZBM (AZB), although structurally unstable, are the likely material basis for an irritating sensation in the mout,. In addition, AZB can play a therapeutic role in Alzheimer's disease, Parkinson's and depression by exerting antioxidant and anti-inflammatory effects. The main targets of AZB are the TRPV1, TRPA1 and PI3K/AKT signalling pathways. This review will discuss the physical and chemical properties of AZB and its use in the treatment of neurodegenerative diseases to provide a reference for the development of ZBM for use in the treatment of neurodegenerative diseases.

Cancer, a common malignant disease, is one of the predominant causes of diseases that lead to death. Additionally, cancer is often detected in advanced stages and cannot be radically cured. Consequently, there is an urgent need for reliable and easily detectable markers to identify and monitor cancer onset and progression as early as possible. Our aim was to systematically review the relevant roles of cathepsin K (CTSK) in various possible cancers in existing studies. CTSK, a well-known key enzyme in the bone resorption process and most studied for its roles in the effective degradation of the bone extracellular matrix, is expressed in various organs. Nowadays, CTSK has been involved in various cancers such as prostate cancer, breast cancer, bone cancer, renal carcinoma, lung cancer and other cancers. In addition, CTSK can promote tumor cells proliferation, invasion and migration, and its mechanism may be related to RANK/RANKL, TGF-β, mTOR and the Wnt/β-catenin signaling pathway. Clinically, some progress has been made with the use of cathepsin K inhibitors in the treatment of certain cancers. This paper reviewed our current understanding of the possible roles of CTSK in various cancers and discussed its potential as a biomarker and/or novel molecular target for various cancers.

Cancer incidence and mortality rates are increasing annually. Treatment with surgery, chemotherapy and radiation therapy (RT) is unsatisfactory because many patients have advanced disease at the initial diagnosis. However, the emergence of immunotherapy promises to be an effective strategy to improve the outcome of advanced tumors. Immune checkpoint antibodies, which are at the forefront of immunotherapy, have had significant success but still leave some cancer patients without benefit. For more cancer patients to benefit from immunotherapy, it is necessary to find new drugs and combination therapeutic strategies to improve the outcome of advanced cancer patients and achieve long-term tumor control or even eradication. Peptides are promising choices for tumor immunotherapy drugs because they have the advantages of low production cost, high sequence selectivity, high tissue permeability, low toxicity and low immunogenicity etc., and the adjuvant matching and technologies like nanotechnology can further optimize the effects of peptides. In this review, we present the current status and mechanisms of research on peptides targeting multiple immune cells (T cells, natural killer (NK) cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), regulatory T cells (Tregs)) and immune checkpoints in tumor immunotherapy; and we summarize the current status of research on peptide-based tumor immunotherapy in combination with other therapies including RT, chemotherapy, surgery, targeted therapy, cytokine therapy, adoptive cell therapy (ACT) and cancer vaccines. Finally, we discuss the current status of peptide applications in mRNA vaccine delivery.

Abstract Circular RNAs (circRNAs) are classified as noncoding RNAs because they are devoid of a 5’ end cap and a 3’ end poly (A) tail necessary for cap-dependent translation. However, increasing numbers of translated circRNAs identified through high-throughput RNA sequencing overlapping with polysome profiling indicate that this rule is being broken. CircRNAs can be translated in cap-independent mechanism, including IRES (internal ribosome entry site)-initiated pattern, MIRES (m6A internal ribosome entry site) -initiated patterns, and rolling translation mechanism (RCA). CircRNA-encoded proteins harbour diverse functions similar to or different from host proteins. In addition, they are linked to the modulation of human disease including carcinomas and noncarcinomas. CircRNA-related translatomics and proteomics have attracted increasing attention. This review discusses the progress and exclusive characteristics of circRNA translation and highlights the latest mechanisms and regulation of circRNA translatomics. Furthermore, we summarize the extensive functions and mechanisms of circRNA-derived proteins in human diseases, which contribute to a better understanding of intricate noncanonical circRNA translatomics and proteomics and their therapeutic potential in human diseases.

Fibrosis, a disease characterized by an excess accumulation of extracellular matrix components, could lead to organ failure and death, and is to blame for up to 45 % of all fatalities in developed nations. These disorders all share the common trait of an unchecked and increasing accumulation of fibrotic tissue in the affected organs, which leads to their malfunction and eventual failure, even if their underlying causes are highly diverse and, in some cases, remain unclear. Numerous studies have identified activated myofibroblasts as the common cellular elements ultimately responsible for the replacement of normal tissues with nonfunctional fibrotic tissue. The transforming growth factor-β pathway, for instance, plays a significant role in practically all kinds of fibrosis. However, there is no specific drug for the treatment of fibrosis, several medications with anti-hepatic fibrosis properties are still in the research and development stages. Peptide, which refers to a substance consisting of 2–50 amino acids, is characterized by structural diversity, low toxicity, biological activities, easy absorption, specific targeting, few side effects, and has been proven to be effective in anti-fibrosis. Here, we summarized various anti-fibrosis peptides in fibrosis including the liver, lungs, kidneys, and other organs. This review will provide a new insight into peptide mediated anti-fibrosis and is helpful to creation of antifibrotic medications.

BackgroundRaw hawthorn (RH) is a traditional Chinese medicine commonly used to treat indigestion. Charred hawthorn (CH) is obtained from RH by charring. It is reported that the effect of CH treatment on dyspepsia is stronger than RH. However, this has not been fully proven. The purpose of this study was to compare the effects of RH and CH on functional dyspepsia (FD) model rats. And contribute to the development of dietary therapy for dyspepsia.MethodsSPF-grade male SD rats were divided into 5 groups: the control group, the model group, the Mos group, the RH group, and the CH group. The FD rat model was established by using the methods of water restriction, fasting, tilting cage restraint, day and night upside down, swimming, and tail damping. The body weight of rats in each group was recorded. And the gastric emptying rate, intestinal propulsive rate, and the levels of motilin (MTL), gastrin (GAS), and 5-HT in serum were compared in each group. The expression of C-kit in the stomach and small intestine of each group was compared by immunofluorescence and PCR.ResultsRH and CH could increase weight, improve the gastric emptying rate and intestinal propulsive rate, and promote the secretion of motilin (MTL), gastrin (GAS), and 5-HT in the serum of FD rats. RH and CH can upregulate the expression of the characteristic protein c-kit of ICC in the stomach and small intestine of FD model rats, and the effect of CH is stronger than RH.ConclusionRH and CH may increase the number of interstitial cells of Cajal (ICC) in the gastrointestinal tract by upregulating c-kit expression, thus improving gastrointestinal motility in FD model rats. And compared with RH, CH has certain advantages.

Supercritical carbon-dioxide (SC-CO2) is a promising two-phase technology for flavor components (volatile oil and alkylamides) extract from Zanthoxylum bungeanum pericarp. However, the gastric protective effect of SC-CO2 extract from Z. bungeanum (SZB) have not been systematically investigated. In this study, response surface methodology (RSM) was employed to optimize the yield of SZB, and the average yield of 11.07 % were obtained under optimal parameters (30 MPa, 43 °C and time 75 min). Here, limonene, linalool and hydroxy-α-sanshool were identified as the main compounds of SZB by GC–MS and UPLC-Q-Extractive Orbitrap/MS analysis. When the gastric protective effect of SZB (5, 10 and 20 mg/kg, p.o.) were evaluated, significant increase in body weight and organ indexes of rat, and decreased gastric lesion were observed. Furthermore, nineteen serum metabolites were regarded as the potential biomarkers for the gastric protective effect of SZB. Collectively, this study provides a comprehensive perspective into the chemical composition analysis and gastric protective effect of Z. bungeanum SC-CO2 extract.

The fruits of Zanthoxylum bungeanum Maxim. Was a popular traditional Chinese herbal medicine for pain relief, itching prevention, and diarrhea relief. The fruits of Zanthoxylum bungeanum Maxim. Essential oil (HEO) had an effect of improving anxiety and other emotional disorders. In this paper, we aim to systematically research the antidepressant effects of HEO on Chronic Mild Unpredictable Stimulation (CUMS) mice and explore the relevant molecular mechanisms. Experimental mice were exposed to CUMS for 8 weeks. Meanwhile, for 8 weeks, Sertraline hydrochloride (20 mg/kg/day) and HEO (50, 100, and 150 mg/kg/day) were administered by gavage. HEO treatment increased residence time of central zone in OFT and open-arm in EPM test but decreased immobility times in FST and TST. Moreover, HEO treatment improved the levels of 5-HT, DA, NE, and BDNF, but reduced CRF and CORT levels of the HPA axis in the hippocampus. Network pharmacology predicted the possible mechanisms for the antidepressant effects of HEO by regulation of PI3K/Akt signaling pathway. The mRNA expression of PI3K and Akt were increased, and immunofluorescence results in the hippocampus indicated that HEO treatment could increase the phosphorylation of PI3K and Akt. Besides, the viability of CORT-treated PC12 cells was significantly improved by HEO treatment. The AO-EB staining, MOMP analysis, and flow cytometry analysis results showed HEO inhibiting the CORT-induced apoptosis in PC12 cells significantly. Besides, the phosphorylation of PI3K and Akt in COTR-induced PC12 cells could increase by HEO treatment. In conclusion, HEO ameliorated depression behavior induced by CUMS, potentially via regulating HPA axis and activating PI3K/Akt signaling pathway to reduce neuronal apoptosis.

Neurodegenerative disease is a progressive neurodegeneration caused by genetic and environmental factors. Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) are the three most common neurodegenerative diseases clinically. Unfortunately, the incidence of neurodegenerative diseases is increasing year by year. However, the current available drugs have poor efficacy and large side effects, which brings a great burden to the patients and the society. Increasing evidence suggests that occurrence and development of the neurodegenerative diseases is closely related to the mitochondrial dysfunction, which can affect mitochondrial biogenesis, mitochondrial dynamics, as well as mitochondrial mitophagy. Through the disruption of mitochondrial homeostasis, nerve cells undergo varying degrees of apoptosis. Interestingly, it has been shown in recent years that the natural agents derived from herbal medicines are beneficial for prevention/treatment of neurodegenerative diseases via regulation of mitochondrial dysfunction. Therefore, in this review, we will focus on the potential therapeutic agents from herbal medicines for treating neurodegenerative diseases via suppressing apoptosis through regulation of mitochondrial dysfunction, in order to provide a foundation for the development of more candidate drugs for neurodegenerative diseases from herbal medicine.

Pyracantha fortuneana (Maxim.) Li has been used as a herbal medicine in China in its long history. Since ancient times, the fruits of P. fortuneana has been considered a functional food to improve various diseases. Many bioactive substances, including proanthocyanidins, phenols, polysaccharides, and dietary fibers, have been isolated and identified from the P. fortuneana, which possess diverse biological properties both in vitro and in vivo. Although the researches on the P. fortuneana have achieved extensive progress, the systematic study of its biological activities is still relatively lacking. In addition, accumulating researches focus on the landscape value of the P. fortuneana and the development of its by-products. The by-products of P. fortuneana, which show good development potentials in the field of agricultural production and environmental protection, are important for improving the economic value of P. fortuneana and its significance. After extensive reviewing and analyzing the existing published articles, books, and patents, this study aims to a systematic and summarized research trends of P. fortuneana and its phytochemical compositions, nutritional values, pharmacological effects and health benefits of its extracts/monomers, which would be beneficial for the future development of this medicinal plant as functional food or drugs.

As the largest internal organ, the liver is the key hub for many physiological processes. Previous research on the liver has been mainly conducted on animal models and cell lines, in which not only there are deficiencies in species variability and retention of heritable material, but it is also difficult for primary hepatocytes to maintain their metabolic functions after in vitro expansion. Because of the increased burden of liver disease worldwide, there is a growing demand for 3D in vitro liver models—Liver Organoids. Based on the type of initiation cells, the liver organoid can be classified as PSC-derived or ASC-derived. Liver organoids originated from ASC or primary sclerosing cholangitis, which are co-cultured in matrix gel with components such as stromal cells or immune cells, and eventually form three-dimensional structures in the presence of cytokines. Liver organoids have already made progress in drug screening, individual medicine and disease modeling with hereditary liver diseases, alcoholic or non-alcoholic liver diseases and primary liver cancer. In this review, we summarize the generation process of liver organoids and the current clinical applications, including disease modeling, drug screening and individual medical treatment, which provide new perspectives for liver physiology and disease research.

Inhibitor of nuclear factor kappa B kinase subunit beta (IKK-β), a specific regulator of nuclear factor-κB (NF-κB), is considered a valid target to design novel drugs to treat rheumatoid arthritis, glomerulonephritis and various cancers. In this study, in order to design and then identify promising compounds targeting IKK-β, a series of reported IKK-β inhibitors were used to develop 3D-QSAR models. Docking-based and minimization-based poses were generated for model construction. CoMSIA model #8 based on docking poses was selected due to its satisfactory internal and external validation results and the sufficient information delivery capability. After a contour map analysis, 41 new designs were depicted based on a graphical design scheme and 25 of them were assessed as eligible for screening. Compound 21MX007 has aroused our attention for its both competitive QSAR-prediction and docking-scoring result. Detailed docking interactions of 21MX007-protein complex were investigated via a deep analysis of docking results and a comparative molecular dynamics simulation. Strong interactions and an extra hydrogen bond which echoes the H-bond requirements of substituent acquired from the design scheme were observed. From MD analysis, 21MX007-protein system was tested. The system was proved to have good stability in terms of a downward trend of RMSD and Rg values and a continuous and stable H-bond interaction and a lower average binding free energy. Thus, compound 21MX007 was successfully identified as a promising IKK-β inhibitor.

Atherosclerosis, as a chronic inflammatory response, is one of the main causes of cardiovascular diseases. Atherosclerosis is induced by endothelial cell dysfunction, migration and proliferation of smooth muscle cells, accumulation of foam cells and inflammatory response, resulting in plaque accumulation, narrowing and hardening of the artery wall, and ultimately leading to myocardial infarction or sudden death and other serious consequences. Flavonoid is a kind of natural polyphenol compound widely existing in fruits with various structures, mainly including flavonols, flavones, flavanones, flavanols, anthocyanins, isoflavones, and chalcone, etc. Because of its potential health benefits, it is now used in supplements, cosmetics and medicines, and researchers are increasingly paying attention to its role in atherosclerosis. In this paper, we will focus on several important nodes in the development of atherosclerotic disease, including endothelial cell dysfunction, smooth muscle cell migration and proliferation, foam cell accumulation and inflammatory response. At the same time, through the classification of flavonoids from fruits, the role and potential mechanism of flavonoids in atherosclerosis were reviewed, providing a certain direction for the development of fruit flavonoids in the treatment of atherosclerosis drugs.

Context Guizhi-Shaoyao-Zhimu decoction (GSZD), a famous ancient oriental Chinese prescription, has been widely used for thousands of years to treat ‘arthromyodynia’. Objective The clinical studies of GSZD for the treatment of gout were systematically reviewed to evaluate its clinical efficacy and safety. Methods All randomized controlled trials (RCTs) related to GSZD and gout were collected starting from the database establishment until 29 February 2020, from the Embase, PubMed, Cochrane Library, Web of Knowledge, VIP and other databases. This systematic review and meta-analysis were performed in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, and all analysis of the test was completed using Stata (SE12.0) and Revman (5.3). Results A total of 535 studies were searched, and 13 studies were included in our meta-analysis (n = 1056 participants). Compared with the conventional western medicine treatments, GSZD treatment yielded a significantly increase in the number of clinically effective patients (OR = 3.67, 95%CI = 2.39–5.64, p = 0.57), an improved mean reduction in the level of uric acid (MD = −54.06; 95% CI = −69.95 to −38.17). Meanwhile, the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and interleukin-6 (IL-6) were also significantly decreased after the GSZD treatment with no increased relative risk of side-effects. Conclusions Our present works suggested that GSZD could be considered as an effective alternative remedy for clinical treatment of gout. In addition, it also provides a scientific basis for GSZD to be better applied in clinic in the future.

Background:Yiqi-Tongluo Capsule (YTC) is a Chinese traditional patent medicine that has been used in the treatment of myocardial ischemia (MI). However, its molecular mechanisms against MI have not been clear.Methods: Network analysis and experimental verification were used to explore the potential molecular mechanisms of YTC for MI treatment. Firstly, the main components in the capsules and the potential targets of these components were predicted by online databases. The MI related genes were collected from Genecards and Online Mendelian Inheritance in Man (OMIM) databases. The drug targets and disease targets were intersected, and then the protein-protein interaction (PPI) and Drug-Molecular-Target-Disease Network (DMTD) were constructed, and GO enrichment analysis and KEGG pathway enrichment analysis were performed. Based on the H2O2-stimulated H9c2 cells, flow cytometry, western blot (WB) and immunofluorescence experiments were performed to verify the network analysis prediction.Results: A total of 100 active components and 165 targets of YTC were predicted, in which there were 109 targets intersected with the targets of MI. GO and KEGG analysis showed that these potential targets were related to a variety of biological processes and molecular mechanisms, including oxidative stress and PI3K/AKT pathway. Astragaloside IV (AS IV) and paeoniflorin (PAE) might be the main active components in YTC. The results of cell counting kit-8 (CCK-8) showed that YTC alleviated the damage of H2O2 to H9c2 cells. The results of flow cytometry, DAPI staining and JC-1 probe showed that YTC alleviated H2O2 induced apoptosis in H9c2 cells. In addition, YTC reduced the level of intracellular superoxide anion, increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA) in H2O2-induced H9c2 cells. The results of immunofluorescence and WB showed that the phosphorylation of PI3K and Akt were increased, the expression of Bcl-2 was up-regulated and the expression of cleaved caspase-3 and Bax were down-regulated. Besides, the nuclear translocation of Nrf2 were increased.Conclusion: In conclusion, the results of this study showed that YTC might alleviate MI by suppressing apoptosis induced by oxidative stress via the PI3K/Akt/Nrf2 signal pathway.

Monoterpene pyridine alkaloids (MTPAs) are alkaloids derived from iridoid glycosides (IGs). The common molecular structure of MTPAs is the pyridine ring, while some of them have a cyclopenta[c]pyridine skeleton. Some compounds containing this structure are potentially bioactive medicinal agents. In this paper, seven drug candidates (A–G), ninety natural source products (1–90), thirty-seven synthesized compounds (91–127), as well as twenty-six key intermediates (S1–S26) were summarized. We categorized five types of MTPAs and one type of cyclopenta[c]pyridine alkaloids in all. Additionally, their possible genetic pathways were proposed. Then, the chemical transformation, biotransformation, chemical synthesis, as well as the bioactivity of MTPAs and cyclopenta[c]pyridine derivatives were analyzed and summarized. Cyclopenta[c]pyridine derivatives can be concisely and chirally synthesized, and they have shown potentials with antibacterial, insecticidal, antiviral, anti-inflammatory, and neuropharmacological activities.

Abstract Cyathulae Radix (CR), also known as “Chuanniux” is a well-known traditional Chinese herbal medicine that has been used in China for thousands of years. The present work reviewed advances in traditional uses, origin, chemical constituents, pharmacology, pharmacokinetics, and toxicity studies of CR. This work aims to provide more up-to-date references for modern study and application of this plant. Furthermore, the possible trends and perspectives for future research of this plant are also discussed. In China, the roots of CR have been widely used in clinical practice to treat orthopedic, gynecological, and urologic diseases. Currently, over 59 compounds have been isolated and identified from CR, including alkaloids and flavonoids. The extracts and compounds from CR have many pharmacological activities both in vivo and in vitro. They provide beneficial effects on the hematological system and anti-inflammatory properties. However, few studies have investigated the pharmacokinetics and toxicity of CR. Further studies should be undertaken to investigate the clinical effects, toxic constituents, and pharmacokinetics of CR; perform quality evaluation; and establish quality criteria for processed C. officinalis. Furthermore, studying the changes of raw and processed CR and the variety of this plant between different cultivated areas and cultivars will be interesting.

Beauvericin (BEA) is a well-known mycotoxin produced by many fungi, including Beaveria bassiana. The purpose of this study was to evaluate the in vitro distribution and metabolism characteristics as well as the in vivo pharmacokinetic (PK) profile of BEA. The in vitro metabolism studies of BEA were performed using rat, dog, mouse, monkey and human liver microsomes, cryopreserved hepatocytes and plasma under conditions of linear kinetics to estimate the respective elimination rates. Additionally, LC-UV-MSn (n = 1~2) was used to identify metabolites in human, rat, mouse, dog and monkey liver microsomes. Furthermore, cytochrome P450 (CYP) reaction phenotyping was carried out. Finally, the absolute bioavailability of BEA was evaluated by intravenous and oral administration in rats. BEA was metabolically stable in the liver microsomes and hepatocytes of humans and rats; however, it was a strong inhibitor of midazolam 1′-hydroxylase (CYP3A4) and mephenytoin 4′-hydroxylase (CYP2C19) activities in human liver microsomes. The protein binding fraction values of BEA were >90% and the half-life (T1/2) values of BEA were approximately 5 h in the plasma of the five species. The absolute bioavailability was calculated to be 29.5%. Altogether, these data indicate that BEA has great potential for further development as a drug candidate. Metabolic studies of different species can provide important reference values for further safety evaluation.

Rheum palmatum L. (RPL) is a known traditional herbal medicine with the functions of “heat-clearing and damp-drying” in traditional Chinese medicine. Its anti-cancer effect against lung cancer has been confirmed previously, but the related mechanisms and active substances for its action has been little studied. This study adopted the network pharmacology, built the network map of drug ingredients and disease targets (DDN), and discussed the effective components of RPL and its possible mechanisms. All constituents of RPL were collected through database search and literature mining, and the potential active constituents were screened. The inverse pharmacophore matching model was used to predict the targets of active ingredients, and the method was supplemented by database retrieval and literature mining. Compounds-target data were inputted into Cytoscape software to build the DDN of RPL, and functional annotation analysis and pathway enrichment analysis were carried out. Finally, 20 active compounds were screened, which acted on 817 targets. A total of 22,418 lung cancer-related targets were collected, and 761 overlapped with drug targets. By bioinformatics annotation of these overlapping genes, a total of 235 gene ontology (GO) functional annotation analyses and 46 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. It was found that the enrichment of GO and KEGG was associated with apoptosis, suggesting RPL plays an anti-lung cancer role via inducing cell apoptosis. Subsequent cell experiment results showed RPL and its active constituents inhibited the proliferation of A549 cells and reduced clone formation rate of A549 cells via induction of apoptosis. In this study, the pharmacodynamic basis and mechanism of RPL against lung cancer were studied from the perspective of systematic pharmacology, which would be beneficial for further elucidating the anticancer effect of RPL on lung cancer.

Zanthoxyli Pericarpium (ZP) are the dried ripe peel of Zanthoxylum schinifolium Sieb. et Zucc (ZC) or Zanthoxylum bungeanum Maxim (ZB). It has wide range of uses both medicine and food, and favorable market value. The diverse specifications of components of ZP is exceptional, and the common aims of adulteration for economic profit is conducted. In this work, a novel method for the identification different species of ZP is proposed using convolutional neural networks (CNNs). The data used for the experiment is 5 classes obtained from camera and mobile phones. Firstly, the data considering 2 categories are trained to detect the labels by YOLO. Then, the multiple deep learning including VGG, ResNet, Inception v4, and DenseNet are introduced to identify the different species of ZP (HZB, DZB, OZB, ZA and JZC). In order to assess the performance of CNNs, compared with two traditional identification models including Support Vector Machines (SVM) and Back Propagation (BP). The experimental results demonstrate that the CNN model have a better performance to identify different species of ZP and the highest identification accuracy is 99.35%. The present study is proved to be a useful strategy for the discrimination of different traditional Chinese medicines (TCMs).

Background: Rheumatoid arthritis (RA) is a known intractable chronic inflammatory disease of synovial joints characterized by hyperplasia and consecutive inflammation with a high prevalence.Guizhi-Shaoyao-Zhimu (GSZD) is the first choice for clinical treatment of RA in Chinese traditional medicine. This study is aimed to explore the possible pharmacological mechanisms of anti-arthritic effect of GSZD. Methods: Type II collagen-induced arthritis (CIA) rat model was used to study the anti-arthritic activity of GSZDin vivo, and toe swelling & arthritis score, serum levels of cytokines, and pathological examinations were carried out. In vitro, TNF-α induced MH7A cells were used to study the possible mechanisms of GSZD. The anti-proliferative effects of GSZD were determined by MMT assay, and pro-apoptotic activity of GSZD in MH7A cells was determined by flow cytometry analysis & DAPI staining. Furthermore, the adhesive and invasive abilities of MH7A cells were determined using cell adhesion and transwell assays. MMPs levels were determined by ELISA assays, and mRNA expressions of Caspase-3, -9, Bax, SOCS1, Bcl-2, JAK2, STAT-3 and -5 were determined using qRT-PCR analysis. Besides, the major chemical components in GSZD were analyzed by HPLC-QqQ-MS analysis. Results: Our results showed GSZD reduced the toe swelling & arthritis score, and serum levels of TNF-α, IL-1β, IL-6 & IL-17a in CIA rats; pathological examination results indicated GSZD improved ankle joint injury in CIA rats.In vitro, GSZD showed significant anti-proliferative and pro-apoptotic effects on TNF-α stimulated MH7A cells. After GSZD treatment, the adhesive and invasive abilities of MH7A cells were reduced, and secretions of MMPs, IL-6 and IL-8 were also reduced. GSZD decreased the releases of TNF-α and IL-1β in LPS stimulated RAW 264.7 cells. Further studies showed GSZD up-regulated mRNA expressions of Caspase-3, -9, Bax, and SOCS1, whereas down-regulated mRNA expressions of Bcl-2, JAK2, STAT3 and STAT5. Besides, 13 major chemical components were identified in GSZD extracts through HPLC-QqQ-MS analysis. Conclusion: Our results suggested GSZD possesses an anti-rheumatic effect on CIA rats, and the possible mechanism is related to inhibiting inflammatory response, inhibiting invasion and migration of synovial fibroblasts, and inducing apoptosis in synovial fibroblasts.

Abstract Melatonin is a widely known hormone in animals. Since melatonin was discovered in plants, more and more studies highlight its involvement in a wide range of physiological processes including plant development and stress responses. Many advances have been made in the terms of melatonin-mediated abiotic stress resistance and innate immunity in plants, focusing on model plants such as rice and Arabidopsis. In this study, 7 melatonin synthesis genes were systematically analyzed in cassava. Quantitative real-time PCR showed that all these genes were commonly regulated by melatonin, flg22, Xanthomonas axonopodis pv manihotis (Xam) and hydrogen peroxide (H2O2). Transient expression in Nicotiana benthamiana revealed the subcellular locations and possible roles of these melatonin synthesis genes. Notably, we highlight novel roles of these genes in hypersensitive-like cell death, as confirmed by the results of several physiological parameters. Moreover, transient expression of these genes had significant effects on the transcripts of reactive oxygen species (ROS) accumulation and defense-related genes, and triggered the burst of callose depositions and papillae-associated plant defense, indicating the possible role of them in plant innate immunity. Taken together, this study reveals the comprehensive transcripts and putative roles of melatonin synthesis genes as well as melatonin in immune responses in cassava.

In the original publication of this article [1], the English official name of the affiliation 1 has been changed to “Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China”.

Pinelliae Rhizoma Praeparatum cum Alumine (PRPCA) is an important traditional processed herbal medicine mainly used for treating phlegm in China for more than 2000 years. In our previous studies, extraction optimization, characterization, and bioactivities of total polysaccharides from PRPCA were investigated. In this study, further purification of these polysaccharides was performed. Two polysaccharides named neutral fraction of total polysaccharides-II (TPN-II) and acidic fraction of total polysaccharides-II (TPA-II) were obtained by gradient ion-exchange chromatography followed by gel-permeation chromatography. Results of scanning electron microscopy (SEM) analysis in the present study showed that TPN-II had a tight structure with a rough and uneven surface, while TPA-II had a relative homogeneous surface and a loose structure. Further studies indicated that TPN-II was a homosaccharide mainly composed by glucose with a molecular weight of 8.0 kDa. TPA-II was mainly composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 2.1, 2.3, 1.7, 10.6, 2.6, 14.2, and 2.5, with a molecular weight of 1250 kDa. The nuclear magnetic resonance (NMR) results indicated that α and β form glycoside bonds existed in TPN-II and TPA-II, and TPN-II was composed of α-glucopyranose. In addition, both purified polysaccharides have significant anti-inflammatory effects on mucus secretion of human airway epithelial NCI-H292 cells without cytotoxicity. Compared with TPN-II, TPA-II exhibited more significant anti-inflammatory effects on lipopolysaccharide (LPS)-induced airway inflammation by regulating levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) and inhibiting mucus secretion. The results suggest that polysaccharides from PRPCA could be explored as therapeutic agents in treating inflammation and over secretion of mucus in asthma.

Red yeast rice (RYR) is made by fermenting the rice with Monascus. It is commonly used in food colorants, dyeing, and wine making in China and its neighboring countries. Nowadays RYR has two forms on the market: common RYR is used for food products, the other form is functional RYR for medicine. However, some researchers reported that commercial lovastatin (structure is consistent with monacolin K) is illegally added to common RYR to meet drug quality standards, so as to imitate functional RYR and sell the imitation at a higher price. Based on current detection methods, it is impossible to accurately distinguish whether functional RYR is adulterated. Therefore, it is especially important to find a way to authenticate functional RYR. In the current review, the advances in history, applications, components (especially monacolins, monacolins detection methods), quality standards, authentication methods and perspectives for the future study of RYR are systematically reviewed.

Xanthium strumarium L. (Asteraceae) is a common and well-known traditional Chinese herbal medicine usually named Cang-Er-Zi, and has been used for thousands of years in China. The purpose of this paper is to summarize the progress of modern research, and provide a systematic review on the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics, and toxicology of the X. strumarium. Moreover, an in-depth discussion of some valuable issues and possible development for future research on this plant is also given. X. strumarium, as a traditional herbal medicine, has been extensively applied to treat many diseases, such as rhinitis, nasal sinusitis, headache, gastric ulcer, urticaria, rheumatism bacterial, fungal infections and arthritis. Up to now, more than 170 chemical constituents have been isolated and identified from X. strumarium, including sesquiterpenoids, phenylpropenoids, lignanoids, coumarins, steroids, glycosides, flavonoids, thiazides, anthraquinones, naphthoquinones and other compounds. Modern research shows that the extracts and compounds from X. strumarium possess wide-ranging pharmacological effects, including anti- allergic rhinitis (AR) effects, anti-tumor effects, anti-inflammatory and analgesic effects, insecticide and antiparasitic effects, antioxidant effects, antibacterial and antifungal effects, antidiabetic effects, antilipidemic effects and antiviral effects. However, further research should focus on investigating bioactive compounds and demonstrate the mechanism of its detoxification, and more reasonable quality control standards for X. strumarium should also be established.

Red pigment (RP) was extracted from the peels of Zanthoxylum bungeanum Maxim (PZB) by ultrasonic-assisted extraction (UAE) in this work. Box–Behnken design–response surface methodology (BBD-RSM) was employed to research the efficiency of the RP extraction. Based on the optimization of RSM, results showed that the optimal extraction conditions were as follows: liquid–solid ratio of 31 mL/g, extraction time of 41 min, and extraction temperature of 27 °C, and under these conditions, the actual absorbance value was 0.615 ± 0.13%, highly agreeing with the predicted value by the model. Furthermore, ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) was used to separate and analyze RP. The compounds of RP were mainly flavonoids, and there were five compounds detected for the first time in PZB. In addition, RP showed significant antioxidant activities in vitro, which could be developed for anti-aging candidate drugs and functional foods. In conclusion, ultrasound-assisted extraction with BBD-RSM and chromatographic separation technology with UPLC-MS are efficient strategies for the isolation and identification of RP from PZB.

Bombyx batryticatus (B. batryticatus), a well-known traditional animal Chinese medicine, has been commonly used in China for thousands of years. The present paper reviewed advances in traditional uses, origin, chemical constituents, pharmacology and toxicity studies of B. batryticatus. The aim of the paper is to provide more comprehensive references for modern B. batryticatus study and application. In Traditional Chinese Medicine (TCM) culture, drugs containing B. batryticatus have been used to treat convulsions, headaches, skin prurigo, scrofula, tonsillitis and fever. Many studies indicate B. batryticatus contains various compounds, including protein and peptides, fatty acids, flavonoids, nucleosides, steroids, coumarin, polysaccharide and others. Numerous investigations also have shown that extracts and compounds from B. batryticatus exert a wide spectrum of pharmacological effects both in vivo and in vitro, including effects on the nervous system, anticoagulant effects, antitumor effects, antibacterial and antifungal effects, antioxidant effects, hypoglycemic effects, as well as other effects. However, further studies should be undertaken to investigate bioactive compounds (especially proteins and peptides), toxic constituents, using forms and the quality evaluation and control of B. batryticatus. Furthermore, it will be interesting to study the mechanism of biological activities and structure-function relationships of bioactive constituents in B. batryticatus.

Zanthoxylum bungeanum Maxim. (Rutaceae) is a popular food additive and traditional Chinese herbal medicine commonly named HuaJiao in China. This plant is widely distributed in Asian countries. The aim of this paper is to provide a systematic review on the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics, and toxicology of this plant. Furthermore, the possible development and perspectives for future research on this plant are also discussed. To date, over 140 compounds have been isolated and identified from Z. bungeanum, including alkaloids, terpenoids, flavonoids, and free fatty acids. The extracts and compounds have been shown to possess wide-ranging biological activity, such as anti-inflammatory and analgesic effects, antioxidant and anti-tumor effects, antibacterial and antifungal effects, as well as regulatory effects on the gastrointestinal system and nervous system, and other effects. As a traditional herbal medicine, Z. bungeanum has been widely used to treat many diseases, especially digestive disorders, toothache, stomach ache, and diarrhea. Many traditional usages of this plant have been validated by present investigations. However, further research elucidating the structure-function relationship among chemical compounds, understanding the mechanism of unique sensation, as well as exploring new clinical effects and establishing criteria for quality control for Z. bungeanum should be further studied.