Neuropharmacological insights into Gardenia jasminoides Ellis: Harnessing therapeutic potential for central nervous system disorders.

BACKGROUND: In China, Gardenia jasminoides Ellis (GJE) has a longstanding history of application. The Ministry of Health has listed it as one of the first pharmaceutical or food resources. In ethnic, traditional, and folk medicine, GJE has been used to treat fever and cold and relieve nervous anxiety. Recent studies have confirmed the significant efficacy of GJE for treating central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder; however, GJE has not been systematically evaluated. PURPOSE: This research systematically summarizes global studies on the use of GJE for treating CNS disorders and explores the potential applications and underlying mechanisms via intestinal flora analysis and network pharmacology, aiming to establish a scientific basis for innovative CNS disorder treatment with GJE. METHODS: The PRISMA guidelines were used, and electronic databases such as the Web of Science, PubMed, and China National Knowledge Infrastructure were searched using the following search terms: "Gardenia jasminoides Ellis" with "central nervous system disease," "neuroprotection," "Alzheimer's disease," "Parkinson's disease," "ischemic stroke," "Epilepsy," and "major depressive disorder." The published literature up to September 2023 was searched to obtain relevant information on the application of GJE for treating CNS disorders. RESULTS: There has been an increase in research on the material formulation and mechanisms of action of GJE for treating CNS disorders, with marked effects on CNS disorder treatment in different countries and regions. We summarized the research results related to the role of GJE in vitro and in vivo via multitargeted interventions in response to the complex mechanisms of action of CNS disorders. CONCLUSION: We systematically reviewed the research progress on traditional treatment for GJE and preclinical mechanisms of CNS disorders and explored the potential of optimizing network pharmacology strategies and intestinal flora analysis to elucidate the mechanisms of action of GJE. The remarkable therapeutic efficacy of GJE, an important resource in traditional medicine, has been well documented in the literature, highlighting its significant medicinal potential.

Withania somnifera root extract inhibits MGO-induced skin fibroblast cells dysfunction via ECM-integrin interaction.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal, known as Ashwagandha, has long been used in traditional medicine in Ayurveda, India, a representative adaptogen. The main active constituents of W. somnifera are withanolides, and the root is often used as a medicine with a wide range of pharmacological activities, which can be used to treat insomnia, neurasthenia, diabetes mellitus and skin cancer. AIM OF THE STUDY: Whole-component qualitative and quantitative analyses were performed on W. somnifera. We explored the ameliorative effect of the adaptogen representative plant W. somnifera on the senescence events of MGO-injured fibroblasts and its action mechanism and verified the hypotheses that WS can inhibit the accumulation of AGEs and regulate the dynamic balance among the components of the ECM by modulating the expression of integrin ß1 receptor; as a result, WS maintains cellular behavioural and biological functions in a normal range and retards the aging of skin from the cellular level. MATERIALS AND METHODS: In this study, the components of WS were first qualitatively and quantitatively analysed by HPLC fingerprinting and LC-MS detection. Second, a model of MGO-induced injury of CML-overexpressing fibroblasts was established. ELISA was used to detect CML expression and the synthesis of key extracellular matrix ECM protein components COL1, FN1, LM5 and TNC synthesis; CCK-8 was used to detect cell viability; EDU was used to detect cell proliferation capacity; fluorescence was used to detect cell adhesion capacity; and migration assay were used to detect cell migration capacity; qRT-PCR was used to detect the regulatory pathway TGF-ß1 and MMP-2, MMP-9 in ECMs; immunofluorescence was used to detect the expression of ITGB1; and WB was used to detect the expression of COL1, FN1, LM5, Tnc, TGF-ß1, MMP-2, MMP-9 and ITGB1. RESULTS: In total, 27 active ingredients were analysed from WS, which mainly consisted of withanolide components, such as withaferin A and withanolide A. Based on the model of MGO-induced fibroblast senescence injury, WS significantly inhibited CML synthesis. By up-regulating the expression of integrin ß1, it upregulated the expression of the TGF-ß1 gene, which is closely related to the generation of ECMs, downregulated the expression of the MMP-2 and MMP-9 genes, which are closely related to the degradation of ECMs, maintained the dynamic balance of the four types of ECMs, and improved cell viability as well as proliferation, migration and adhesion abilities. CONCLUSIONS: WS can prevent cellular behavioural dysfunction and delay skin ageing by reducing the accumulation of CML, upregulating the expression of the ITGB1 receptor, maintaining the normal function of ECM-integrin receptor interaction and preventing an imbalance between the production and degradation of protein components of ECMs. The findings reported in this study suggest that WS as a CML inhibitor can modulate ECM-integrin homeostasis and has great potential in the field of aging retardation.

The effect of vine tea (Ampelopsis grossedentata) extract on fatigue alleviation via improving muscle mass.

ETHNOPHARMACOLOGICAL RELEVANCE: Vine Tea (VT, Ampelopsis grossedentata), boasts a venerable tradition in China, with a recorded consumption history exceeding 1200 years. Predominantly utilized by ethnic groups in southwest China, this herbal tea is celebrated for its multifaceted therapeutic attributes. Traditionally, VT has been employed to alleviate heat and remove toxins, exhibit anti-inflammatory properties, soothe sore throats, lower blood pressure, and fortify bones and muscles. In the realm of functional foods derived from plant resources, VT has garnered attention for its potential in crafting anti-fatigue beverages or foods, attributed to its promising efficacy and minimal side effects. Currently, in accordance with the Food Safety Standards set forth by the Monitoring and Evaluation Department of the National Health and Family Planning Commission in China, VT serves as a raw material in various beverages. AIM OF THE STUDY: VT has an anti-fatigue or similar effect in folk. However, the underlying molecular mechanisms contributing to VT's anti-fatigue effects remain elusive. This study endeavors to investigate the influence of Vine Tea Aqueous Extract (VTE) on fatigue mitigation and to elucidate its operative mechanisms, with the objective of developing VTE as a functional beverage. MATERIALS AND METHODS: The preparation of VTE involved heat extraction and freeze-drying processes, followed by the identification of its metabolites using UPLC-QTOF-MS to ascertain the chemical composition of VTE. A fatigue model was established using a forced swimming test in mice. Potential molecular targets were identified through network pharmacology, transcriptome analysis, and molecular docking. Furthermore, RT-PCR and Western blot techniques were employed to assess mRNA and protein expressions related to the AMPK and FoxO pathways. RESULTS: VTE significantly prolonged the duration of swimming time in an exhaustive swimming test in a dose-dependent manner, while simultaneously reducing the concentrations of blood lactic acid (LA), lactate dehydrogenase (LDH), serum urea nitrogen (SUN), and creatine kinase (CK). Notably, the performance of the high-dose VTE group surpassed that of the well-recognized ginsenoside. VTE demonstrated a regulatory effect akin to ginsenoside on the AMPK energy metabolism pathway and induced downregulation in the expression of Gadd45α, Cdkn1a, FOXO1, and Fbxo32 genes, suggesting an enhancement in skeletal muscle mass. These findings indicate that VTE can improve energy metabolism and muscle mass concurrently. CONCLUSIONS: VTE exhibits significant anti-fatigue effects, and its mechanism is intricately linked to the modulation of the AMPK and FoxO pathways. Crucially, no caffeine or other addictive substances with known side effects were detected in VTE. Consequently, vine tea shows substantial promise as a natural resource for the development of anti-fatigue beverages within the food industry.

[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.

A comprehensive review of vine tea: Origin, research on Materia Medica, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Vine tea is a popular folk tea that has been consumed in China for more than 1200 years. It is often used in ethnic medicine by ethnic groups in southwest China with at least 35 aliases in 10 provinces. In coastal areas, vine tea is mostly used to treat heatstroke, aphtha, aphonia, toothache, etc. In contrast, in the southwest inland regions, vine tea is mostly used to clear away heat and toxic materials, antiphlogosis and relieving sore-throat, lowering blood pressure and lipid levels, and alleviating fatigue. Three main species have been used as the source of vine tea, Nekemias grossedentata, Nekemias cantonensis and Nekemias megalophylla. Among them, the leaves of Nekemias grossedentata were considered as new food resource in complicance with regulations, according to the Food Safety Standards published by the Monitoring and Evaluation Department of the National Health and Family Planning Commission in China. AIM OF THE STUDY: At present, the comprehensively summary of Materia Medica on the history and source of vine tea is currently unavailable. The current article summed up the Materia Medica, species origin and pharmacological effects of all 3 major species used in vine tea to fill the knowledge gaps. We also aim to provide a reference for future research on historical textual, resource development and medicinal utilization of vine tea. MATERIALS AND METHODS: Adhering to the literature screening methodology outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this review encompasses 148 scholarly research papers from three database, paper ancient books, local chronicles and folklore through field investigations. We then comprehensively summarized and discussed research progresses in scientific and application studies of vine tea. RESULTS: The historical records indicated that vine tea could have been used as early as Southern and Northern Dynasties (AC 420-589). Nekemias grossedentata, Nekemias cantonensis and Nekemias megalophylla, were used to considered as vine tea in the ethnic medicine. The main phytochemicals found in three plants are flavonoids, polyphenols and terpenoids, among which dihydromyricetin (DHM) is the most important and most studied active substance. The key words "Ampelopsis grossedentata" (Synonym of Nekemias grossedentata) and "dihydromyricetin/DHM" showed the highest frequency over the last 27 year based on the research trend analysis. And the ethnopharmacology studies drawn the main activities of vine tea are antioxidant, antibacterial, hepatoprotective, neuroprotective and anti-atherosclerosis activities. CONCLUSIONS: This review systematically summarized and discussed vine tea from the following five aspects, history, genetic relationship, phytochemistry, research trend and ethnopharmacology. Vine tea has a long historical usage in Chinese ethnic medicine. Its outstanding therapeutic efficacies have attracted extensive attention in other places in the world at present. Nekemias cantonensis and Nekemias megalophylla are quite similar to Nekemias grossedentata in terms of many aspects. However, the current research has a narrow focus on mainly Nekemias grossedentata and DHM. We propose that future studies could be carried out to determine the synergistic effect of multi-components and multi-targets of vine tea including all 3 species to provide valuable knowledge.

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.

[Research progress on chemical constituents of Schisandra chinensis and its effect on nonalcoholic fatty liver disease].

Schisandra chinensis, a traditional Chinese medicinal herb, is rich in chemical constituents, including lignans, triterpenes, polysaccharides, and volatile oils. Clinically, it is commonly used to treat cardiovascular, cerebrovascular, liver, gastrointestinal, and respiratory diseases. Modern pharmacological studies have shown that S. chinensis extract and monomers have multiple pharmacological activities in lowering liver fat, alleviating insulin resistance, and resisting oxidative stress, and have good application prospects in alleviating nonalcoholic fatty liver disease(NAFLD). Therefore, this study reviewed the research progress on chemical constituents of S. chinensis and its effect on NAFLD in recent years to provide references for the research on S. chinensis in the treatment of NAFLD.

'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.

Bibliometric Study of Adaptogens in Dermatology: Pharmacophylogeny, Phytochemistry, and Pharmacological Mechanisms.

Background: Adaptogens are a class of medicinal plants that can nonspecifically enhance human resistance. Most of the plant adaptogens have relevant applications in dermatology, but there are still few studies related to their particular action and co-operative mechanisms in topical skin application. Methods: Plant adaptogens related articles and reviews that published between 1999 and 2022 were obtained from the Web of Science Core Collection database. Various bibliographic elements were collected, including the annual number of publications, countries/regions, and keywords. CiteSpace, a scientometric software, was used to conduct bibliometric analyses. Also, the patsnap global patent database was used to analyze the patent situation of plant adaptogens in the field of cosmetics up to 2021. Results: We found that the effects of plant adaptogens on skin diseases mainly involve atopic dermatitis, acne, allergic contact dermatitis, psoriasis, eczema, and androgenetic alopecia, etc. And the effects on skin health mainly involve anti-aging and anti-photoaging, anti-bacterial and anti-fungal, anti-inflammatory, whitening, and anti-hair loss, etc. Also, based on the results of patent analysis, it is found that the effects of plant adaptogens on skin mainly focus on aging retardation. The dermatological effects of plant adaptogens are mainly from Fabaceae Lindl., Araliaceae Juss. and Lamiaceae Martinov., and their mainly efficacy phytochemical components are terpenoids, phenolic compounds and flavonoids. Conclusion: The plant adaptogens can repair the skin barrier and maintain skin homeostasis by regulating the skin HPA-like axis, influencing the oxidative stress pathway to inhibit inflammation, and regulating the extracellular matrix (ECM) components to maintain a dynamic equilibrium, ultimately achieving the treatment of skin diseases and the maintenance of a healthy state.

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.

Protective effects of flavonoids in Coreopsis tinctoria Nutt. in a mouse model of type 2 diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Coreopsis tinctoria Nutt., a popular tea drink used in the Xinjiang region of China, has been traditionally used to treat diabetes and chronic metabolic diseases in China, Portugal, and North America. The bioactive extraction and potential mechanism have not been fully elucidated until now. AIM OF THE STUDY: Traditional herbal medicines usually share network targets due to multicomponent therapeutics. Therefore, we tried to explore the protective effects of C. tinctoria on diabetes and the related molecular mechanism. MATERIALS AND METHODS: A flavonoid-rich fraction of C. tinctoria (CTF) was prepared. After 15 weeks of continuous treatment with CTF, the blood glucose and blood lipid levels of experimental mice were evaluated. Tissue was collected for differentially expressed genes (DEGs), bioinformatics analysis, RT‒PCR and Western blot for target-related DEGs. RESULTS: After 15 weeks of continuous treatment with CTF, db/db mice showed reversed levels of glucose, insulin, glucagon and glycated hemoglobin A1c. CTF treatment also regulated total cholesterol, triglycerides, low density lipoprotein, nonesterified fatty acid, alanine transaminase, and aspartate transaminase. Major metabolic pathways were found to be dysregulated in the liver using a combined analysis of transcriptomics and network pharmacology. CTF treatment regulated 48.2% of 6357 dysregulated genes in db/db mice. The mitochondrial electron transport chain and tricarboxylic acid cycle were mainly affected. The sequencing data showed that fifty-nine predicted target genes for CTF were reverse regulated. Together with 1528 coexpressed genes, these genes reflected the main characteristics of the whole perturbed transcriptomic profile, i.e., dysregulated mitochondrial metabolism. The important genes of the target and coexpressed genes were further verified at the gene and protein levels. CONCLUSIONS: The results confirm that the metabolic changes induced by hyperglycemia are closely related to mitochondrial metabolism in the liver. CTF alters a core gene set that exerts regulatory effects at the biological pathway level in db/db mice. In conclusion, our data reveal that an important molecular event for CTF treatment is the regulation of mitochondrial metabolism and support the idea that herbs or natural compounds are potential therapeutic substances for mitochondrial dysfunction-related diabetes.

A comprehensive review on traditional and modern research of the genus Bupleurum (Bupleurum L., Apiaceae) in recent 10 years.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Bupleurum (family Apiaceae), comprising approximately 248 accepted species, is widely distributed and used in China, Japan, India, Central Asia, North Africa and some European countries as traditional herbal medicines. Certain species have been reported to have significant therapeutic effects in fever, inflammatory disorders, cancer, gastric ulcer, virus infection and other diseases. AIM OF THE REVIEW: we performed a comprehensive review of the ten-year research progress in phytochemistry, pharmacology, toxicity, along with bibliometrics research of the genus Bupleurum, aiming to identify knowledge gaps for future research. MATERIALS AND METHODS: All the literatures are retrieved from library and electronic sources including Web of Science, PubMed, Elsevier, Google Scholar, CNKI and Baidu Scholar. These papers cover studies of the traditional use, phytochemistry, pharmacology, and toxicology of the genus Bupleurum. RESULTS: There is a long history of using the genus Bupleurum in traditional herbal medicine that dated back to over 2000 years ago. Twenty-five species and 8 varieties with 3 variants within this genus have been reported to be effective to treat fever, pain, liver disease, inflammation, thoracolumbar pain, irregular menstruation and rectal prolapse. The main phytochemicals found in these plants are triterpene saponins, volatile oil, flavonoid, lignans, and polysaccharides. Many of these compounds have also been shown to have anti-inflammatory, anti-tumor, antimicrobial, immunoregulation, neuroregulation, hepatoprotective and antidiabetic activities. Meanwhile, improper usage of Bupleurum may induce cytotoxic effects, and polyacetylenes may be the main poisonous compounds. CONCLUSIONS: This article summarized recent findings about Bupleurum research from many different aspects. While a small number of Bupleurum species have been investigated through modern pharmacology methods, there are still major knowledge gaps due to inadequate studies and ambiguous findings. Future research could focus on more specific phytochemistry studies combined with mechanistic analysis to provide better guidance to utilize Bupleurum as medicinal resources.

[Degradation kinetics of ß-nicotinamide mononucleotide based on reliable HPLC quantitative method].

To explore the stability characteristics of ß-nicotinamide mononucleotide(NMN) and provide data support for NMN production, preparation, and related product development, this study established a simple HPLC content determination method for NMN in simple substrate and investigated the degradation behavior, degradation products, and degradation kinetics of NMN under various chemical, physical, and biological conditions. The HPLC method employed a Welch Xtimate AQ-C_(18) column(4.6 mm×250 mm, 5 µm), a detection wavelength of 266 nm, a column temperature of 30 ℃, a flow rate of 1.0 mL·min~(-1), an injection volume of 5 µL, and a mobile phase consisting of methanol(A) and a 10 mmol·L~(-1) ammonium formate aqueous solution(B) with a gradient elution(0-6.7 min, 0-4% A; 6.7-13 min, 4%-18% A; 13-14.2 min, 18% A; 14.2-15 min, 18%-0 A; 15-22 min, 0 A). This method provided good separation between NMN and potential impurities and degradation products, and had a wide linear range, short analysis time, good durability, high accuracy, an average sample recovery rate of 98.71%, and an RSD of 1.2%. The instrument precision had an RSD of 0.26%, and the linearity within the examined range was excellent(R~2≥0.999 9). This method can be applied for NMN content determination in simple substrate. The degradation process of NMN in aqueous solution followed apparent first-order kinetics, with the degradation rate primarily influenced by high temperature and pH. NMN was more stable in low-temperature, neutral, or weakly acidic/alkaline environments. Strong acids or strong alkalis could accelerate its degradation, and its degradation rate was less affected by pepsin and trypsin. In an aqueous solution at room temperature, it followed the kinetic equation lg C_t=0.005 7t + 4.817 2, with t_(0.9) and t_(1/2) values of 95.58, 860.26 h, respectively. The results suggest that pH and temperature are the main factors affecting the stability of NMN in aqueous solution, and low temperature, moisture protection, and a weakly acidic environment are more conducive to the storage and application of NMN and its products.

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.

Research progress of Chinese herbal medicine compounds and their bioactivities: Fruitful 2020.

Traditional Chinese medicines (TCMs) have continued to be a treasure trove. The study of chemodiversity and versatility of bioactivities has always been an important content of pharmacophylogeny. There is amazing progress in the discovery and research of natural components with novel structures and significant bioactivities in 2020. In this paper we review 271 valuable natural products, including terpenoids, steroids, flavonoids, phenylpropanoids, phenolics, nitrogen containing compounds and essential oil, etc., isolated and identified from TCMs published in journals of Chinese Traditional and Herbal Drugs (Zhong Cao Yao) and Chinese Herbal Medicines (CHMs), and focus on their structures, source organisms, and relevant bioactivities, paying special attention to structural characteristics of novel compounds and newly revealed pharmacological properties of known compounds. It is worth noting that natural products with antitumor activity still constitute the primary object of research. Among the reported compounds, two new triterpenoids, i.e., ursolic acid 3-O-ß-cis-caffeate and mollugoside E, display remarkable cytotoxicity against PC-9 and HL-60 cell lines, respectively. Three known phenolic compounds, i.e., pyoluteorin, 4-hydroxy-3-methoxy cinnamaldehyde and 3,7-dimethoxy-5-hydroxy-1,4-phenanthrenequinone, exhibit significant cytotoxicity against multiple cell lines. Numerous studies on the free radical scavenging activity of reported compounds are currently underway. In vitro, three known phenolic compounds, i.e., 3,4-O-dicaffeoylquinic acid methyl ester, 3,4,5-O-tricaffeoylquinic acid methyl ester and arbutin, had more considerable antioxidant activities than vitamin C. The anti-inflammatory, anti-diabetic, hypolipidemic, neuroprotective and antimicrobial activities of isolated compounds are also encouraging. The structural characteristics and bioactivities of TCM compounds highlighted here reflect the enormous progress of CHM research in 2020 and will play a positive role in the future drug discovery and development. According to pharmacophylogeny, the phylogenetic distribution of compounds with different natures and flavors can be explored, with view to better mining TCM resources.

Anti-asthmatic fraction screening and mechanisms prediction of Schisandrae Sphenantherae Fructus based on a combined approach.

Objective: Schisandrae Sphenantherae Fructus (SSF) is a traditional Chinese medicine used to treat coughs and pulmonary inflammatory diseases. However, the pharmacodynamic material basis and mechanisms for SSF in asthma treatment remain unclear. This study aims to screen the anti-asthmatic fraction and verify the pharmacodynamic material basis, predict the potential mechanism, and verify the interaction ability between compounds and core targets. Methods: First, three fractions from SSF were compared in terms of composition, comparison, and anti-asthmatic effects. Then, the ultra-performance liquid chromatography-quadrupole/time-of-flight-mass spectrometry/mass spectrometry (UPLC-Q/TOF-MS/MS) strategy was used to identify the compounds from the active fraction, and the anti-asthmatic efficacy of the active fraction was further studied by the ovalbumin (OVA)-induced asthma murine model. Finally, network pharmacology and molecular methods were used to study the relationships between active compounds, core targets, and key pathways of PEF in asthma treatments. Results: The petroleum ether fraction (PEF) of SSF showed better effects and could significantly diminish lung inflammation and mitigate the level of serum immunoglobulin E (IgE), interleukin (IL)-4, IL-5, IL-6, IL-13, and IL-17 in mice. A total of 26 compounds from the PEF were identified, among which the main compounds are lignans and triterpenes. Moreover, 21 active compounds, 129 overlap-ping targets, and 10 pathways were screened by network pharmacology tools. The top five core targets may play a great role in asthma treatment. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the PEF can treat asthma by acting on multiple asthma pathological processes, including the IL-17 signaling pathway, T helper (Th) 17 cell differentiation, and the calcium signaling pathway. Molecular docking was performed to evaluate the interactions of the protein-ligand binding, and most docked complexes had a good binding ability. Conclusion: The present results might contribute to exploring the active compounds with anti-asthmatic activity.

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.

The genus Chrysanthemum: Phylogeny, biodiversity, phytometabolites, and chemodiversity.

The ecologically and economically important genus Chrysanthemum contains around 40 species and many hybrids and cultivars. The dried capitulum of Chrysanthemum morifolium (CM) Ramat. Tzvel, i.e., Flos Chrysanthemi, is frequently used in traditional Chinese medicine (TCM) and folk medicine for at least 2,200 years. It has also been a popular tea beverage for about 2,000 years since Han Dynasty in China. However, the origin of different cultivars of CM and the phylogenetic relationship between Chrysanthemum and related Asteraceae genera are still elusive, and there is a lack of comprehensive review about the association between biodiversity and chemodiversity of Chrysanthemum. This article aims to provide a synthetic summary of the phylogeny, biodiversity, phytometabolites and chemodiversity of Chrysanthemum and related taxonomic groups, focusing on CM and its wild relatives. Based on extensive literature review and in light of the medicinal value of chrysanthemum, we give some suggestions for its relationship with some genera/species and future applications. Mining chemodiversity from biodiversity of Chrysanthemum containing subtribe Artemisiinae, as well as mining therapeutic efficacy and other utilities from chemodiversity/biodiversity, is closely related with sustainable conservation and utilization of Artemisiinae resources. There were eight main cultivars of Flos Chrysanthemi, i.e., Hangju, Boju, Gongju, Chuju, Huaiju, Jiju, Chuanju and Qiju, which differ in geographical origins and processing methods. Different CM cultivars originated from various hybridizations between multiple wild species. They mainly contained volatile oils, triterpenes, flavonoids, phenolic acids, polysaccharides, amino acids and other phytometabolites, which have the activities of antimicrobial, anti-viral, antioxidant, anti-aging, anticancer, anti-inflammatory, and closely related taxonomic groups could also be useful as food, medicine and tea. Despite some progresses, the genetic/chemical relationships among varieties, species and relevant genera have yet to be clarified; therefore, the roles of pharmacophylogeny and omics technology are highlighted.

Mining Therapeutic Efficacy from Treasure Chest of Biodiversity and Chemodiversity: Pharmacophylogeny of Ranunculales Medicinal Plants.

Ranunculales, comprising of 7 families that are rich in medicinal species frequently utilized by traditional medicine and ethnomedicine, represents a treasure chest of biodiversity and chemodiversity. The phylogenetically related species often have similar chemical profile, which makes them often possess similar therapeutic spectrum. This has been validated by both ethnomedicinal experiences and pharmacological investigations. This paper summarizes molecular phylogeny, chemical constituents, and therapeutic applications of Ranunculales, i.e., a pharmacophylogeny study of this representative medicinal order. The phytochemistry/metabolome, ethnomedicine and bioactivity/pharmacology data are incorporated within the phylogenetic framework of Ranunculales. The most studied compounds of this order include benzylisoquinoline alkaloid, flavonoid, terpenoid, saponin and lignan, etc. Bisbenzylisoquinoline alkaloids are especially abundant in Berberidaceae and Menispermaceae. The most frequent ethnomedicinal uses are arthritis, heat-clearing and detoxification, carbuncle-abscess and sore-toxin. The most studied bioactivities are anticancer/cytotoxic, antimicrobial, and anti-inflammatory activities, etc. The pharmacophylogeny analysis, integrated with both traditional and modern medicinal uses, agrees with the molecular phylogeny based on chloroplast and nuclear DNA sequences, in which Ranunculales is divided into Ranunculaceae, Berberidaceae, Menispermaceae, Lardizabalaceae, Circaeasteraceae, Papaveraceae, and Eupteleaceae families. Chemical constituents and therapeutic efficacy of each taxonomic group are reviewed and the underlying connection between phylogeny, chemodiversity and clinical uses is revealed, which facilitate the conservation and sustainable utilization of Ranunculales pharmaceutical resources, as well as developing novel plant-based pharmacotherapy.