Corrigendum to "Dark tea: A popular beverage with possible medicinal application" [Chinese Herbal Medicines 15 (2023) 3315036].

[This corrects the article DOI: 10.1016/j.chmed.2022.08.005.].

[Prediction of quality markers and medicinal value of sea buckthorn leaves based on network pharmacology, content determination, and activity evaluation].

The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.

Integration of network pharmacology, transcriptomics and molecular docking reveals two novel hypoglycemic components in snow chrysanthemum.

Our previous studies uncovered the glucose-lowering properties of snow chrysanthemum tea, however, the active ingredients and underlying mechanisms were yet to be uncovered. Flavonoids are the most active and abundant components in snow chrysanthemum tea. In this study, we treated leptin-deficient diabetic ob/ob or high-fat diet (HFD)-induced C57BL/6 J obese mice with or without total flavonoids of snow chrysanthemum (TFSC) for 14 weeks. Results indicated that TFSC ameliorated dyslipidemia and fatty liver, thereby reducing hyperlipidemia. Further mechanism experiments, including RNA-seq and experimental validation, revealed TFSC improved glycolipid metabolism primarily by activating the AMPK/Sirt1/PPARγ pathway. Additionally, by integrating UPLC, network pharmacology, transcriptomics, and experimental validation, we identified two novel hypoglycemic compounds, sulfuretin and leptosidin, in TFSC. Treatment with 12.5 µmol/L sulfuretin obviously stimulated cellular glucose consumption, and sulfuretin (3.125, 6.25 and 12.5 µmol/L) significantly mitigated glucose uptake damage and reliably facilitated glucose consumption in insulin-resistant HepG2 cells. Remarkably, sulfuretin interacted with the ligand-binding pocket of PPARγ via three hydrogen bond interactions with the residues LYS-367, GLN-286 and TYR-477. Furthermore, a concentration of 12.5 µmol/L sulfuretin effectively upregulated the expression of PPARγ, exhibiting a comparable potency to a renowned PPARγ agonist at 20 µmol/L. Taken together, our findings have identified two new hypoglycemic compounds and revealed their mechanisms, which significantly expands people's understanding of the active components in snow chrysanthemum that have hypoglycemic effects.

'Food and medicine continuum' in the East and West: Old tradition and current regulation.

Food-medicine products are important materials for daily health management and are increasingly popular in the global healthy food market. However, because of the biocultural difference, food-medicine knowledge may differ among regions, which hinders the global sharing of such health strategies. Aim at bridging the food-medicine knowledge in the East and West, this study traced the historical roots of food and medicine continuum of the East and West, which was followed by a cross-cultural assessment on the importance of food-medicine products of China, thereafter, the current legislative terms for food-medicine products were studied using an international survey. The results show that the food and medicine continuum in the East and West have their historical roots in the traditional medicines since antiquity, and the food-medicine knowledge in the East and West differs substantially; although the food-medicine products have common properties, their legislative terms are diverse globally; with proofs of traditional uses and scientific evidence, food-medicine products are possible for cross-cultural communication. Finally, we recommend facilitating the cross-cultural communication of the food-medicine knowledge in the East and West, thus to make the best use of the traditional health wisdom in the globe.

Investigating the chemical profile of Rheum lhasaense and its main ingredient of piceatannol-3'-O-ß-D-glucopyranoside on ameliorating cognitive impairment.

Rheum lhasaense A. J. Li et P. K. Hsiao, a stout herb plant from the Polygonaceae, is a typical Tibetan folk herb with heat-clearing and detoxifying effects, but does not have the typical laxative effect compared with other rhubarb plants. Nevertheless, its chemical composition and pharmacological activities still lack in-depth research. The present study endeavored to analyze the possible phytochemical constituents in R. lhasaense and explore the main compound piceatannol-3'-O-ß-D-glucopyranoside (PG) effect on cognitive impairment and its underlying mechanism. The chemical profile of R. lhasaense discovered 46 compounds, including 27 stilbenoids and 13 gallotannins using UPLC-Q-TOF-MS/MS. The UPLC determined the contents of 6 main stilbenoids, among which the content of PG was the highest, up to 61.06 mg/g. Moreover, behavioral tests showed that PG (40 mg/kg and 160 mg/kg) administration markedly ameliorated memory impairments of scopolamine-induced mice. Biochemical parameters showed that PG treatment alleviated the levels of Ach, AchE, and inflammatory factors while elevating the levels of antioxidants in mice. In addition, network pharmacology was performed to reveal PG exert an mild cognitive impairment effect by participating in neurodegenerative disease pathways, proliferation and apoptosis-, and inflammation-related pathways. Eventually, the results of molecular docking and the qRT-PCR revealed that PG down-regulated the mRNA expressions of MMP3, MMP9 and BACE1 in cognitive impairment mice brain tissue. In conclusion, our results demonstrated that PG mitigated scopolamine-induced cognitive dysfunction in mice by targeting the BACE1-MMP3/9 pathway, and PG might be a promising mild AD drug candidate.

Novel active compounds and the anti-diabetic mechanism of mulberry leaves.

Mulberry (Morus alba L.) leaves have long been considered beneficial in traditional Chinese medicine to treat infectious and internal diseases. Recently studies have discovered that the mulberry leaf's total flavonoids (MLF) display excellent hypoglycemia properties. However, the active ingredients and their molecular mechanisms are still uncharacterized. In this study, we explored the hypoglycemic effects of MLF and mulberry leaf polysaccharides (MLP) on ob/ob mice, an animal model of type 2 diabetes mellitus (T2DM), compared with Ramulus Mori (Sangzhi) alkaloid (RMA). Network pharmacology was employed to identify the potential available targets and active compounds of MLF and RMA against hyperglycemia. Molecular docking, an insulin-resistant cell model and qPCR were employed to verify the antidiabetic activity of the critical compounds and the gene expression profiles of the top molecular targets. Here, the results showed that MLF and MLP improved glucose uptake in insulin-resistant hepatocytes. MLF, MLP and RMA alleviated insulin resistance and glucose intolerance in ob/ob mice. Unlike MLF and MLP, RMA administration did not influence the accumulation of intrahepatic lipids. Network pharmacology analysis revealed that morusin, kuwanon C and morusyunnansin L are the main active compounds of MLF and that they amend insulin resistance and glycemia via the PI3K- Akt signaling pathway, lipid and atherosclerosis pathways, and the AGE-RAGE signaling pathway. Moreover, 1-deoxynojirimycin (DNJ), fagomine (FA), and N-methyl-1-deoxynojirimycin are the primary active ingredients of RMA and target carbohydrate metabolism and regulate alpha-glucosidase activity to produce a potent anti-diabetic effect. The molecular docking results indicated that morusin, kuwanon C and morusyunnansin L are the critical bioactive compounds of MLF. They had high affinities with the key targets adenosine A1 receptor (ADORA1), AKT serine/threonine kinase 1 (AKT1), peroxisome proliferator-activated receptor gamma (PPARγ), and glycogen synthase kinase 3 beta (GSK3ß), which play crucial roles in the MLF-mediated glucose-lowering effect. Additionally, morusin plays a role in amending insulin resistance of hepatocytes by repressing the expression of the ADORA1 and PPARG genes. Our results shed light on the mechanism behind the glucose-lowering effects of MLF, suggesting that morusin, kuwanon C, and morusyunnansin L might be promising drug leads for the management of T2DM.

Integrating network pharmacology analysis and pharmacodynamic evaluation for exploring the active components and molecular mechanism of moutan seed coat extract to improve cognitive impairment.

Paeonia suffruticosa (Moutan) is a traditional medicinal plant in China. Its seed coat is rich in resveratrol oligomer, especially suffruticosol B (SB). Previous studies had shown that the seed coat extracts of Paeonia suffruticosa (PSCE) had good cholinesterase inhibitory activity and neuroprotective effect, but the effective dose range was unknown, and the pharmacodynamic components and molecular mechanism of PSCE had not been discussed. The current study aimed to screen the pharmacodynamic components in PSCE and investigate the improvement effect of PSCE and the selected SB on scopolamine-induced cognitive dysfunction in mice and its mechanism. The results of high-throughput sequencing and bioinformatics analysis showed that suffruticosol B (SB) and trans-gnetin H (GH) might be the main active components of PSCE; PSCE might improve cognitive dysfunction through p53, HIF-1, MAPK, and PI3K-Akt signaling pathways, while SB and GH might improve cognitive dysfunction through HIF-1 signaling pathway. SB and GH had good molecular docking activity with the target of HIF-1 signaling pathway. The pharmacodynamic activities of PSCE and SB were further verified by behavioral experiments. PSCE and SB could improve the recognition ability of familiar and new objects and shorten the escape latency in the Morris Water Maze test (PSCE 120 mg∙kg-1, p < 0.05; SB 60 mg∙kg-1, p < 0.01); PSCE and SB could increase Ach and GSH levels, enhance the activities of ChAT, SOD and CAT, decrease the levels of IL-1ß, IL-6, and TNF-α, and decrease the activity of AChE. In conclusion, the results indicated that PSCE might exert pharmacodynamic activity through multiple components, targets, and pathways, and SB and GH might be the main active components of PSCE. PSCE and SB might improve cognitive dysfunction by regulating cholinergic, antioxidant, and anti-inflammatory effects. These results indicated that PSCE and SB might be potential anti-AD drug candidates, providing a scientific basis for the development and utilization of Moutan bark.

Distribution of Therapeutic Efficacy of Ranunculales Plants Used by Ethnic Minorities on the Phylogenetic Tree of Chinese Species.

The medicinal properties of plants can be evolutionarily predicted by phylogeny-based methods, which, however, have not been used to explore the regularity of therapeutic effects of Chinese plants utilized by ethnic minorities. This study aims at exploring the distribution law of therapeutic efficacy of Ranunculales plants on the phylogenetic tree of Chinese species. We collected therapeutic efficacy data of 551 ethnomedicinal species belonging to five species-rich families of Ranunculales; these therapeutic data were divided into 15 categories according to the impacted tissues and organs. The phylogenetic tree of angiosperm species was used to analyze the phylogenetic signals of ethnomedicinal plants by calculating the net relatedness index (NRI) and nearest taxon index (NTI) in R language. The NRI results revealed a clustered structure for eight medicinal categories (poisoning/intoxication, circulatory, gastrointestinal, eyesight, oral, pediatric, skin, and urinary disorders) and overdispersion for the remaining seven (neurological, general, hepatobiliary, musculoskeletal, otolaryngologic, reproductive, and respiratory disorders), while the NTI metric identified the clustered structure for all. Statistically, NRI and NTI values were significant in 5 and 11 categories, respectively. It was found that Mahonia eurybracteata has therapeutic effects on all categories. iTOL was used to visualize the distribution of treatment efficacy on species phylogenetic trees. By figuring out the distribution of therapeutic effects of Ranunculales medicinal plants, the importance of phylogenetic methods in finding potential medicinal resources is highlighted; NRI, NTI, and similar indices can be calculated to help find taxonomic groups with medicinal efficacy based on the phylogenetic tree of flora in different geographic regions.

Plant Pharmacophylogeny: Review and Future Directions.

Medicinal plants have provided numerous medicinal active ingredients for thousands of years and these ingredients have been used in Chinese medicine (CM) and traditional pharmacologies worldwide. Recently, the exploitation and utilisation of medicinal plant resources has increased significantly. The results of the studies have led to the identification of many active components, such as steroidal alkaloids, saponins, terpenoids, and glycosides, in various medicinal plants with different evolutionary levels. Moreover, research on the chemical classification, molecular phylogeny, and pharmacological activity of medicinal plants is increasing in popularity. Pharmacophylogeny is an interdisciplinary topic that studies the correlation between plant phylogeny, chemical composition, and curative effects (pharmacological activity and the traditional curative effect) of medicinal plants. In addition, it provides the basic tools to enable research and development of CM resources. This literature review, based on the genetic relationship between phytogroup and species, highlights the formation process, research content, applications, and future directions of pharmacophylogeny.

[Material basis and mechanism of Huangqin Tea in prevention of colorectal cancer based on network pharmacology and molecular docking].

Colorectal cancer is a malignancy with high mortality. Huangqin Tea(HQT) can exert potential preventive and therapeutic effects on colorectal cancer. Flavonoids are the main compounds in HQT, but the pharmacodynamic material basis and mechanism are unclear. Network pharmacology and molecular docking were used to predict and analyze the targets and signaling pathways of HQT in the prevention and treatment of colorectal cancer. The active components of flavonoids in HQT were searched and screened out by literature review and FAFDrugs4. The related targets of active components were predicted by SwissTargetPrediction, STITCH, and TCMSP. Colorectal cancer-related genes were collected from OMIM, TTD, and GeneCards. The common targets were obtained as the potential targets of HQT in the prevention and treatment of colorectal cancer. Metascape was used for GO function enrichment and KEGG pathway enrichment analyses. Cytoscape was used to construct the protein-protein interaction(PPI) network and "component-target-disease-pathway" network to obtained and analyze core targets and key components. AutoDock Vina was used for molecular docking verification of key components and core targets. The results showed that apigenin, luteolin, wogonin, and baicalein were presumedly the key active components in the prevention and treatment of colorectal cancer, and core targets included TP53, AKT1, VEGFA, PIK3 CA, and SRC. The key KEGG signaling pathways mainly involved PI3 K-AKT, AGE-RAGE, p53, NF-κB, Wnt, Hippo, and calcium signaling pathways. Further molecular docking results showed that four key components showed strong hydrogen bonding ability with the five core targets. This study preliminarily reveals the pharmacodynamic material basis and potential mechanism of HQT in the prevention and treatment of colorectal cancer and provides a theoretical and scientific basis for the application of HQT.

Dissection of full-length transcriptome and metabolome of Dichocarpum (Ranunculaceae): implications in evolution of specialized metabolism of Ranunculales medicinal plants.

Several main families of Ranunculales are rich in alkaloids and other medicinal compounds; many species of these families are used in traditional and folk medicine. Dichocarpum is a representative medicinal genus of Ranunculaceae, but the genetic basis of its metabolic phenotype has not been investigated, which hinders its sustainable conservation and utilization. We use the third-generation high-throughput sequencing and metabolomic techniques to decipher the full-length transcriptomes and metabolomes of five Dichocarpum species endemic in China, and 71,598 non-redundant full-length transcripts were obtained, many of which are involved in defense, stress response and immunity, especially those participating in the biosynthesis of specialized metabolites such as benzylisoquinoline alkaloids (BIAs). Twenty-seven orthologs extracted from trancriptome datasets were concatenated to reconstruct the phylogenetic tree, which was verified by the clustering analysis based on the metabolomic profile and agreed with the Pearson correlation between gene expression patterns of Dichocarpum species. The phylogenomic analysis of phytometabolite biosynthesis genes, e.g., (S)-norcoclaurine synthase, methyltransferases, cytochrome p450 monooxygenases, berberine bridge enzyme and (S)-tetrahydroprotoberberine oxidase, revealed the evolutionary trajectories leading to the chemodiversity, especially that of protoberberine type, aporphine type and bis-BIA abundant in Dichocarpum and related genera. The biosynthesis pathways of these BIAs are proposed based on full-length transcriptomes and metabolomes of Dichocarpum. Within Ranunculales, the gene duplications are common, and a unique whole genome duplication is possible in Dichocarpum. The extensive correlations between metabolite content and gene expression support the co-evolution of various genes essential for the production of different specialized metabolites. Our study provides insights into the transcriptomic and metabolomic landscapes of Dichocarpum, which will assist further studies on genomics and application of Ranunculales plants.

[Withania somnifera: a kind of food-medicine plant popular in world in recent years].

Withania somnifera, also known as Indian ginseng, is an important traditional medicine in the Ayurvedic medical system of India, which has a significant effect of adaptation. Modern studies have shown that the main chemical components of W. somnifera are withanolides, which have antioxidant, anti-tumor, enhancing immunity, cardiovascular protection, neuroprotection, anti-stress, anti-stress reaction and hypoglycemic activities. Studies on human, animal, mutagenesis, genotoxicity, reproductive toxicity and drug interaction showed that W. somnifera had good safety. Clinical trials have proved that W. somnifera is effective in treating a variety of human diseases. As a famous traditional medicine and modern dietary supplement, it has a high reputation and market in the international health product market, but in China, there is little scientific research, market development, product introduction and application. In this paper, the traditional application, chemical composition, pharmacological activity, safety evaluation and clinical study of the plant were introduced, so as to increase the understanding of the dual use of the plant, and to provide reference for the future introduction of the product, the service to the health of the Chinese people and the promotion of the "double cycle" of the trade of health products between China and the international community.

Metabolite Profiling Based on UPLC-Q-TOF-MS/MS and the Biological Evaluation of Medicinal Plants of Chinese Dichocarpum (Ranunculaceae).

The genus Dichocarpum is endemic to East Asia, and many species have been used to treat various diseases. However, phytochemical researches of this genus have been limited to date. In the present study, a metabolomic approach based on UPLC-Q-TOF-MS/MS was used to explore the phytochemical profiles of 10 Chinese Dichocarpum species, and cannabinoid receptor (CB1/CB2) agonistic activities evaluation of these plants was performed. A total of 128 features were putatively annotated, belonging to alkaloids, flavonoids, triterpenes saponins, phenolic acids, and others. Semi-quantitative statistics demonstrated that alkaloids and flavonoids were widely distributed, with the former the most abundant, whereas triterpenes saponins were mainly distributed in D. fargesii and D. wuchuanense. The phylogenetic results obtained from DNA sequencing assigned the 10 species to three groups. Further results of in silico annotation revealed three chemical families and helped determine the characteristic features of the three groups. In addition, the plant extracts of nine species from this genus showed agonistic activity on CB2 receptors. This comprehensive analysis revealed the chemotype distribution and pharmacophylogenetic relationship, to provide clues for the prospective resource utilization of the medicinal plants from the genus Dichocarpum.

Comparative and phylogenetic analyses of the chloroplast genomes of species of Paeoniaceae.

Plants belonging to family Paeoniaceae are not only economically important ornamental plants but also medicinal plants used as an important source of traditional Chinese medicine. Owing to the complex network evolution and polyploidy evolution of this family, its systematics and taxonomy are controversial and require a detailed investigation. In this study, three complete chloroplast genomes of sect. Paeonia, one of the sections of Paeonia, were sequenced and then analysed together with 16 other published chloroplast genomes of Paeoniaceae species. The total lengths of the chloroplast genomes of these species were 152,153-154,405 bp. A total of 82-87 protein-coding genes, 31-40 tRNA genes and 8 rRNA genes were annotated. Bioinformatics analysis revealed 61-74 simple sequence repeats (SSRs) in the chloroplast genomes, most of which have A/T base preference. Codon usage analysis showed that A/U-ending codons were more positive than C/G-ending codons, and a slight bias in codon usage was observed in these species. A comparative analysis of these 19 species of Paeoniaceae was then conducted. Fourteen highly variable regions were selected for species relationship study. Phylogenetic analysis revealed that the species of sect. Paeonia gathered in one branch and then divided into different small branches. P. lactiflora, P. anomala, P. anomala subsp. veitchii and P. mairei clustered together. P. intermedia was related to P. obovata and P. obovata subsp. willmottiae. P. emodi was the sister to all other species in the sect. Paeonia.

[Application and modern research progress of sea buckthorn leaves].

Sea buckthorn(Hippophae rhamnoides) is widely distributed, with abundant resources, a long history of application, and rich nutrition and high medicinal value. Therefore, it has attracted extensive attention from researchers at home and abroad. The focus of attention is mainly on sea buckthorn fruit, but with weak research and development of sea buckthorn leaves. In order to develop and utilize abundant resources of sea buckthorn leaves, this paper systematically reviewed domestic and foreign literatures and summarized the current application, harvesting and processing, chemical constituents and pharmacological activities of sea buckthorn leaves. Sea buckthorn leaves have a wide development and utilization value in food raw materials(like a substituting-for-tea plant), pharmaceutical raw materials and animal feed. Modern studies have shown that the leaves of sea buckthorn are rich in polysaccharides, flavonoids, polyphenols, triterpenes and steroids, as well as vitamins(especially vitamin C), proteins, amino acids and mineral elements. It has various pharmacological effects, such as anti-obesity, hypoglycemia, anti-oxidation, antibacterial, anti-inflammatory and anti-cardiovascular diseases. Domestic and foreign studies have showed that sea buckthorn leaves have important development and utilization prospects, and are worth further study and development.

Artemisia scoparia: Traditional uses, active constituents and pharmacological effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia scoparia Waldst.et Kit (A. scoparia), is an important medicinal plant mainly distributed in China, Korea, Japan, Pakistan, India, Central Europe, Saudi Arabia and Iran. It has been used for a long history to treat fever, inflammation, jaundice, and infection, but systematic reviews about the medicinal uses of A. scoparia are still lacking. AIM OF THE STUDY: This review is to provide up-to-date information on A. scoparia, including its botanical characteristics, medicinal resources, traditional uses, phytochemistry and pharmacological effects, in exploring therapeutic and scientific potentials. MATERIALS AND METHODS: The information related to this article was systematically collected from the scientific literature databases including PubMed, Google Scholar, Web of Science, Science Direct, Springer, China National Knowledge Infrastructure, local books, PhD and MS dissertations, and other web sources. RESULTS: Herein a total of 102 compounds, such as flavonoids, coumarins, chromones, steroids, volatile oil and phenolic acid isolated from A. scoparia are summarized. Among these compounds, the effects of flavonoids, coumarins and phenolic acids were extensively studied. We have comprehensively summarized modern pharmacological studies on A. scoparia and demonstrated A. scoparia and its active components have a wide range of pharmaceutical activities, such as anticancer, anti-inflammatory, antibacterial, liver protection, antiatherogenic, antiviral as well as neuroprotective functions. CONCLUSIONS: As an important Chinese medicinal plant, modern pharmacological studies have demonstrated that A. scoparia has diverse bioactivities, especially on liver protection and anti-inflammatory activities. These prominent bioactivities highlight prospects on new drug development. Nevertheless, the comprehensive evaluation, long-term in vivo toxicity, and clinical efficacy of A. scoparia require further in-depth research.

Stilbenoids isolated from the roots of Rheum lhasaense under the guidance of the acetylcholinesterase inhibition activity.

Four unknown stilbenoids, including one dimer, namely 4'-methoxy-scirpusin A (5) and three monomeric stilbene glycosides, namely piceatannol-3'-O-[2''-(3,5-dihydroxy-4-methoxybenzoyl)]-ß-D-glucopyranoside (13), piceatannol-3'-O-(2''-galloyl)-ß-D-glucopyranoside (14) and piceatannol-3'-O-(6″-p-coumaroyl)-ß-D-glucopyranoside (16) together with 15 described compounds, were isolated from the ethyl acetate fraction of the ethanol extract of roots of Rheum lhasaense based on the guidance of the inhibitory effect on acetylcholinesterase. The structures of the unknown compounds were established by combined spectroscopic analysis and comparing their spectral data with compounds with similar structures. Some selected components were also investigated for their inhibitory abilities on acetylcholinesterase (AChE), indicating that compound 13 may be responsible for higher inhibitory activity of the ethyl acetate fraction on AChE.

Traditional uses, ten-years research progress on phytochemistry and pharmacology, and clinical studies of the genus Scutellaria.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria (Lamiaceae), which includes approximately 360-469 accepted species, is widespread in Europe, North America, East Asia, and South America. Several species have a long history being used as traditional medicines to treat respiratory, peptic, neurological, and hepatic and gall diseases. The phytochemistry and pharmacology of the genus Scutellaria have been developed dramatically in the past ten years, and the traditional uses and clinical studies of the genus have not been systematically summarized. Therefore, it is especially valuable to review the current state of knowledge to provide a basis for further exploration of its medicinal potential. AIM OF THE REVIEW: The review aims to provide updated information on the ethnopharmacology, the ten-year research progress of phytochemistry and pharmacology, and clinical studies of Scutellaria and to explore the potential medicinal values and further studies of Scutellaria. MATERIALS AND METHODS: This review is based on published studies and books from the library and electronic sources, including SciFinder, Scopus, PubMed, Web of Science, Baidu Scholar, CNKI, the online ethnobotanical database, and ethnobotanical monographs. This literature is related to ethnopharmacology, the ten-year research progress on the phytochemistry and pharmacology, and clinical studies of Scutellaria. RESULTS: A total of 50 species, 5 subspecies and 17 varieties of the genus Scutellaria are used as traditional medicine with various biological activities. In the past ten years, 208 chemical constituents have been identified from 16 species and 1 variety of the genus Scutellaria, such as neo-clerodane diterpenoids, sesterterpenoids, terpenoids, flavonoids. Pharmacological research has demonstrated that the extracts and compounds identified from this genus exhibit extensive biological activities, including anticancer, antioxidant, anti-inflammatory, antiviral and antibacterial activities, effects on cardiovascular, cerebrovascular diseases as well as hepatoprotective and neuroprotective effects. The species S. baicalensis, S. barbata, and S. lateriflora and the main compounds baicalein, baicalin and wogonin are involved in clinical trials, which point the way for us to conduct further studies, such as study on the anticancer, antihypertensive, anti-infective, anti-inflammatory, neuroprotective and other effects of Scutellaria. CONCLUSIONS: The species included in the genus Scutellaria can be used to treat cancer, infection, hepatic disorders, cardiovascular and cerebrovascular diseases, neurodegenerative diseases, and other diseases. Some indications in traditional medicines have been confirmed by modern pharmacological studies, such as anticancer, anti-inflammatory, anti-infective activity, and hepatoprotective and neuroprotective effects. The available literature indicated that most of the bioactivities could be attributed to flavonoids and neo-clerodane diterpenoids. Although there are some uses of Scutellaria in clinical practice, the existing research on this genus is still limited. In order to expand the development of medicinal resources of Scutellaria, the already studied species in this genus are recommended for more comprehensive investigation on their active substances, pharmacological mechanisms, quality control, clinical use and new drug research. Additionally, it is necessary to study species that their chemical composition or pharmacological activity have not yet been investigated, especially those used in folk medicine.

Genus Paeonia: A comprehensive review on traditional uses, phytochemistry, pharmacological activities, clinical application, and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia, which comprises approximately 52 shrubs or herbaceous perennials around the world, is the only genus of the Paeoniaceae and is pervasively distributed in Asia, southern Europe, and North America. Many species of the genus Paeonia have been used for centuries in ethnomedical medical systems. AIM OF THE REVIEW: The present study aims to summarize the traditional uses, clinical applications, and toxicology of the genus Paeonia, to critically evaluate the state-of-the-art phytochemical and pharmacological studies of this genus published between 2011 and 2020, and to suggest directions for further in-depth research on Paeonia medicinal resources. MATERIALS AND METHODS: Popular and widely used databases such as PubMed, Scopus, Science Direct, and Google Scholar were searched using the various search strings; from these searches, a number of citations related to the traditional uses, phytochemistry, biological activities, clinical application, and toxicology of the genus Paeonia were retrieved. RESULTS: The use of 21 species, 2 subspecies, and 7 varieties of the genus Paeonia as traditional herbal remedies has been reported, and many ethnomedicinal uses, such as the treatment of hematemesis, blood stasis, dysmenorrhea, amenorrhea, epilepsy, spasms, and gastritis, have been recorded. The roots and root bark are the most frequently reported parts of the plants used in medicinal applications. In phytochemical investigations, 451 compounds have been isolated from Paeonia plants to date, which contains monoterpenoid glucosides, flavonoids, tannins, stilbenes, triterpenoids and steroids, and phenols. Studies of their pharmacological activities have revealed the antioxidant, anti-inflammatory, antitumour, antibacterial, antiviral, cardiovascular protective, and neuroprotective properties of the genus Paeonia. In particular, some bioactive extracts and compounds (total glucosides of peony (TGP), paeonol, and paeoniflorin) have been used as therapeutic drugs or tested in clinical trials. In addition to the "incompatibility" of the combined use of "shaoyao" and Veratrum nigrum L. roots in traditional Chinese medicine theory, Paeonia was considered to have no obvious toxicity based on the available toxicological tests. CONCLUSION: A large number of phytochemical and pharmacological reports have indicated that Paeonia is an important medicinal herb resource, and some of its traditional uses including the treatment of inflammation and cardiovascular diseases and its use as a neuroprotective agent, have been partially confirmed through modern pharmacological studies. Monoterpenoid glucosides are the main active constituents. Although many compounds have been isolated from Paeonia plants, the biological activities of only a few of these compounds (paeoniflorin, paeonol, and TGP) have been extensively investigated. Some paeoniflorin structural analogues and resveratrol oligomers have been preliminarily studied. With the exception of several species (P. suffruticosa, P. ostii, P. lactiflora, and P. emodi) that are commonly used in folk medicine, many medicinal species within the genus do not receive adequate attention. Conducting phytochemical and pharmacological experiments on these species can provide new clues that may lead to the discovery of medicinal resources. It is necessary to identify the effective phytoconstituents of crude extracts of Paeonia that displayed pharmacological activities by bioactivity-guided isolation. In addition, comprehensive plant quality control, and toxicology and pharmacokinetic studies are needed in the future studies.

Traditional uses, phytochemistry, pharmacology, and toxicology of Coreopsis tinctoria Nutt.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Coreopsis tinctoria Nutt. (family Asteraceae) is an important traditional medicine in North America, Europe, and Asia for quite a long historical period, which has received great attention due to its health-benefiting activities, including disinfection, treatment sexual infection, diarrhoea, acute and chronic dysentery, red-eye swelling as well as pain, heat, thirst, hypertension, palpitation, gastrointestinal discomfort, and loss of appetite. AIM OF THE REVIEW: The purpose of this review is to give an overview of the current phytochemistry and pharmacological activities of C. tinctoria, and reveals the correlation among its traditional uses, phytochemistry, pharmacological profile, and potential toxicity. MATERIALS AND METHODS: This review is based on published studies and books from electronic sources and library, including the online ethnobotanical database, ethnobotanical monographs, Scopus, SciFinder, Baidu Scholar, CNKI, and PubMed. These reports are related to the traditional uses, phytochemistry, pharmacology, and toxicology of C. tinctoria. RESULTS: Coreopsis tinctoria is traditionally used in diarrhoea, infection, and chronic metabolic diseases. From 1954 to now, more than 120 chemical constituents have been identified from C. tinctoria, such as flavonoids, polyacetylenes, polysaccharides, phenylpropanoids, and volatile oils. Flavonoids are the major bioactive components in C. tinctoria. Current research has shown that its extracts and compounds possess diverse biological and pharmacological activities such as antidiabetes, anti-cardiovascular diseases, antioxidant, anti-inflammatory, protective effects on organs, neuroprotective effects, antimicrobial, and antineoplastic. Studies in animal models, including acute toxicity, long-term toxicity, and genotoxicity have demonstrated that Snow Chrysanthemum is a non-toxic herb, especially for its water-soluble parts. CONCLUSIONS: Recent findings regarding the main phytochemical and pharmacological properties of C. tinctorial have confirmed its traditional uses in anti-infection and treatment of chronic metabolic disease and, more importantly, have revealed the plant as a valuable medicinal plant resource for the treatment of a wide range of diseases. The available reports indicated that most of the bioactivities in C. tinctorial could be attributed to flavonoids. However, higher quality studies on animals and humans studies are required to explore the efficacy and mechanism of action of C. tinctoria in future.