Alzheimer’s disease (AD) is the leading cause of dementia, yet current therapies provide limited clinical benefit. Neuroinflammation, as an early and sustained driver of AD, places the NLRP3 inflammasome at the center of pathological and therapeutic focus. In this review, we synthesize recent advances in the structure, assembly, and activation of the NLRP3 inflammasome, and evaluate its contribution to AD using evidence from human brain tissues, cerebrospinal fluid, and diverse AD animal models. Available data consistently support aberrant NLRP3 activation in AD brain, where it is closely associated with amyloid-β (Aβ) deposition, tau pathology, glial reactivity, and cognitive decline. We further discuss the cell-type-specific roles of microglia and astrocytes, highlighting microglia as the principal effector cells in inflammasome-associated pathology. Mechanistically, Aβ and tau converge on NLRP3 activation through interconnected pathways involving K+ efflux, lysosomal rupture, mitochondrial dysfunction, and impaired autophagy. Downstream IL-1β, IL-18, and gasdermin D amplify neuroinflammation and neuronal injury. We summarize emerging therapeutic strategies directly targeting its core components or downstream effectors, as well as anti-AD agents with indirect NLRP3 modulation including endogenous molecules, repurposed drugs, and natural products. Collectively, this review regards NLRP3 inflammasome as a critical inflammatory hub and a promising target for disease-modifying therapy in AD, and provide useful perspectives on AD pathogenesis and inform the development of more rational therapeutic strategies.

ETHNOPHARMACOLOGICAL RELEVANCE:Corni fructus are the fruits of Cornus officinalis Sieb. et Zucc. and is widely used in traditional Chinese Medicine for the treatment of dementia. Cornuside, derived from Corni fructus, has been shown to be effective in improving cognition of AD mouse. AIM:In the present study, we investigated the effect of cornuside on cognitive dysfunction and microglial NLRP3 inflammasome activation, as well as explored the underlying mechanism with respect to Sirt1 and autophagy. METHODS:AD mice were established and then treated with cornuside (3, 10, and 30 mg/kg) for 2 weeks. A series of behavioral tests were performed to assess cognition, including the Morris water maze, Y maze, nest building, step-down and step-through tests. Nissl staining was used to evaluate neuronal structural damage. LPS-stimulated BV2 cells were used for in vitro experiments. The anti-inflammatory effects of cornuside on cytokines and NLRP3 inflammasome activation were assessed using ELISA, RT-PCR, immunohistochemistry, western blotting, and immunofluorescence assays. To further elucidate the relationship between Sirt1, autophagy, and NLRP3 inflammasome activation, EX527 and 3-MA were used to inhibit Sirt1 and block autophagy flux in vitro, respectively. RESULTS:Cornuside significantly improved various behavioral performance and inhibited NLRP3 inflammasome activation in LPS-induced mice, as evidenced by decreased levels of NLRP3, ASC, pro-caspase1, caspase1, pro-IL-1β, IL-1β, GSDMD, GSDMD-NT and IL-18. Similar inhibitory effects of cornuside on NLRP3 inflammasome activation was also detected in LPS stimulated BV2 cells. The involvement of Sirt1 and autophagy were further explored in-vivo and in-vitro, revealing that cornuside increased the expression of Sirt1 and enhanced autophagy, with decreased SQSTM1/p62 and increased LC3BII. However, the inhibitory effect of cornuside on NLRP3 inflammasome activation was abrogated by 3-MA, and the effects of cornuside on promoting autophagy and inhibiting NLRP3 inflammasome activation was abolished by EX527. CONCLUSION:Cornuside exerts therapeutic effects on LPS induced AD mice by inhibiting microglial activation and NLRP3 inflammasome overactivation. And Sirt1 mediated autophagy activation is a vital mechanism by which cornuside degrades NLRP3 inflammasome, thereby alleviating neuroinflammation and improving cognitive function.

Achyranthes bidentata Blume (ABB; Chinese name: Huai Niuxi) and Cyathula officinalis K.C.Kuan (COK; Chinese name: Chuan Niuxi), two botanical drugs collectively termed “Niuxi” in traditional Chinese medicine (TCM), are widely used for rheumatoid arthritis (RA) management. This review comprehensively summarized the pharmacological mechanisms and therapeutic potential of the metabolites of ABB and COK on RA, while addressing limitations of current evidence. Of the 314 and 185 metabolites contained in ABB and COK, respectively, 22 metabolites (including Chikusetsusaponin V and chikusetsusaponin Ⅳa), showed multiple anti-RA activities. The mechanisms underlying the effects of ABB and COK with respect to the occurrence and development of RA (including inflammatory processes, immunoregulation, fibroblast-like synoviocytes, angiogenesis, oxidative stress, cartilage degradation, and bone destruction) were evaluated (Graphical Abstract). Numerous signaling pathways, such as the nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), are involved in RA. The metabolites contained in ABB and COK have significant medicinal value and potential in the treatment of RA, while in-depth mechanism studies and clinical research are warranted to support the clinical application of these metabolites.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which mitochondrial dysfunction and neuroinflammation play crucial roles in its progression. Our previous studies found that cornuside from Cornus officinalis Sieb.Et Zucc is an anti-AD candidate, however, its underlying mechanism remains unknown. In the present study, AD mice were established by intracerebroventricular injection of Aβ1−42 and treated with cornuside (3, 10, 30 mg/kg) for 2 weeks. Cornuside significantly ameliorated behavioral deficits, protected synaptic plasticity and relieved neuronal damage in Aβ1−42 induced mice. Importantly, cornuside decreased NLRP3 inflammasome activation, characterized by decreased levels of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β. Furthermore, cornuside promoted mitophagy accompanied by decreasing SQSTM1/p62 and promoting LC3B-I transforming into LC3B-II, via Pink1/Parkin signaling instead of FUNDC1 or BNIP3 pathways. In order to investigate the relationship between NLRP3 inflammasome and mitophagy in the neuroprotective mechanism of cornuside, we established an in-vitro model in BV2 cells exposed to LPS and Aβ1−42. And cornuside inhibited NLRP3 inflammasome activation and subsequent cytokine release, also protected neurons from damaging factors in microenvironment of conditional culture. Cornuside improved mitochondrial function by promoting oxidative phosphorylation and glycolysis, decreasing the production of ROS and mitochondrial membrane potential depolarization. Besides, mitophagy was also facilitated with increased colocalization of MitoTracker with LC3B and Parkin, and Pink1/Parkin, FUNDC1 and BNIP3 pathways were all involved in the mechanism of cornuside. By blocking the formation of autophagosomes by 3-MA, the protective effects on mitochondria, the inhibition on NLRP3 inflammasome as well as neuronal protection in conditional culture were eliminated. There is reason to believe that the promotion of mitophagy plays a key role in the NLRP3 inhibition of cornuside. In conclusion, cornuside re-establishes the mitophagy flux which eliminates damaged mitochondria and recovers mitochondrial function, both of them are in favor of inhibiting NLRP3 inflammasome activation, then alleviating neuronal and synaptic damage, and finally improving cognitive function.

Cornuside has been discovered to improve learning and memory in AD mice, however, its underlying mechanism was not fully understood. In the present study, we established an AD mice model by intracerebroventricular injection of Aβ1-42, which were treated with cornuside (3, 10, 30 mg/kg) for 2 weeks. Cornuside significantly ameliorated cognitive function of AD mice in series of behavioral tests, including Morris water maze test, nest building test, novel object recognition test and step-down test. Additionally, cornuside could attenuate neuronal injury, and promote cholinergic synaptic transmission by restoring the level of acetylcholine (ACh) via inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as facilitating choline acetyltransferase (ChAT). Furthermore, cornuside inhibited oxidative stress levels amplified as decreased malondialdehyde (MDA), by inhibiting TXNIP expression, improving total anti-oxidative capacity (TAOC), raising activities of superoxide dismutase (SOD) and catalase (CAT). Cornuside also reduced the activation of microglia and astrocytes, decreased the level of proinflammatory factors TNF-α, IL-6, IL-1β, iNOS and COX2 via interfering RAGE-mediated IKK-IκB-NF-κB phosphorylation. Similar anti-oxidative and anti-inflammatory effects were also found in LPS-stimulated BV2 cells via hampering RAGE-mediated TXNIP activation and NF-κB nuclear translocation. Virtual docking revealed that cornuside could interact with the active pocket of RAGE V domain directly. In conclusion, cornuside could bind to the RAGE directly impeding the interaction of Aβ and RAGE, and cut down the expression of TXNIP inhibiting ROS production and oxidative stress, as well as hamper NF-κB p65 mediated the inflammation.

Ethnopharmacological relevance: Cornus officinalis Sieb. et Zucc. is a medicinal and edible homolog in traditional Chinese medicine. Loganin, an iridoid glycoside, is one of the main active components of Cornus officinalis Sieb. et Zucc. Loganin has been demonstrated to improve depression-like behavior and may be a potential antidepressant candidate. However, the pharmacokinetic characteristics and tissue distribution of loganin, especially in the brain region, are still unclear.Aim of the study: This study aims to investigate the pharmacokinetic characteristics and tissue distribution after oral administration of loganin in rats.Materials and methods: A simple, rapid and reproducible UPLC-MS/MS method was developed and validated for the determination of loganin in rat plasma and tissues. The samples were prepared by acetonitrile precipitation with chloramphenicol as internal standard (IS). Loganin was separated by gradient elution on ACQUITY UPLC (R) BEH C18 (2.1 x 50 mm, 1.7 mu m) using multiple reactions monitoring (MRM) mode. Concentration-time data was subjected to pharmacokinetic analysis. The pharmacokinetic parameters of loganin in rat plasma were analyzed by compartment model using DAS 2.0 software.Results: The established UPLC-MS/MS method was accurate and reliable with a good linearity (R-2 > 0.99) in the respective concentration range, satisfying the quantitative requirements. This method was successfully used to study the pharmacokinetics and tissue distribution after oral administration of loganin in rats. The peak time (T-max) of oral administration was about 40 min, and the half-life (t(1/2)) was about 50 min, indicating that loganin was quickly absorbed and eliminated in rats. Oral bioavailability was 5.50%. The dose correlation results showed that AUC had a poor correlation with dose, while C-max had a good correlation with dose. In tissues, loganin (35 mg/kg) was highly distributed in the stomach, small intestine, kidney, liver and lung. When the dose was 70 mg/kg, loganin had significant distribution in the cortex.Conclusion: In this study, a simple and sensitive UPLC-MS/MS method was developed and validated for the determination of loganin in rat plasma and tissues. Loganin was absorbed quickly, eliminated quickly, and had low bioavailability. The distribution of loganin in the cortex was higher than that in the hippocampus. We hope that our results can provide a reference for loganin to become a new antidepressant.

Phytochemical investigation of the roots of Euphorbia ebracteolata Hayata resulted in the isolation of three new rosane diterpenoids, euphebracteolatins C-E (1-3), along with fourteen known analogs (4-17). Their structures were determined on the basis of extensive spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR. Euphebracteolatin C (1) contains a C-1/C-10 double bond and a keto group at C-7, and euphebracteolatins D and E (2-3) possess an aromatic ring-A in their skeleton. The plausible biogenetic pathways of all the isolates were also proposed. Furthermore, compounds 1 and 9 showed selective cytotoxicity against HepG2 cells with IC50 values of 14.29 and 12.33 μM, respectively, and 2-3 displayed moderate cytotoxicity against three human cancer lines, with IC50 values ranging from 23.69 to 39.25 μM.

Increasing evidence suggests that the failure of clinical antidepressants may be related with neuroinflammation. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is an intracellular multiprotein complex, and has been considered as a key contributor to the development of neuroinflammation. Inhibition of NLRP3 inflammasome is an effective method for depression treatment. In this review, we summarized current researches highlighting the role of NLRP3 inflammasome in the pathology of depression. Firstly, we discussed NLRP3 inflammasome activation in patients with depression and animal models. Secondly, we outlined the possible mechanisms driving the activation of NLRP3 inflammasome. Thirdly, we discussed the pathogenetic role of NLRP3 inflammasome in depression. Finally, we overviewed the current and potential antidepressants targeting the NLRP3 inflammasome. Overall, the inhibition of NLRP3 inflammasome activation may be a potential therapeutic strategy for inflammation-related depression.

Anti‐Alzheimer's disease (AD) drugs can only change the symptoms of cognitive impairment in a short time but cannot prevent or completely cure AD. Thus, a more effective drug is urgently needed. Cornuside is extracted from Corni Fructus, a traditional Chinese medicine that plays an important role in treating dementia and other age‐related diseases. Thus, the study aimed to explore the effects and mechanisms of Cornuside on the D‐galactose (D‐Gal) induced aging mice accompanied by cognitive decline. Initially, we found that Cornuside improved the learning and memory abilities of D‐Gal‐treated mice in behavioral experiments. Pharmacological experiments indicated that Cornuside acted on anti‐oxidant and anti‐inflammatory effects. Cornuside also reversed acetylcholin esterase (AChE) activity. Meanwhile, pathology tests showed that Cornuside had a protective effect on neuron damage. Cornuside increased the expression of brain‐derived neurotrophic factor (BDNF), and down‐regulated the expression of receptor for advanced glycosylation end products (RAGE), ionized calcium binding adapter molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP) respectively. Further studies claimed that Cornuside had important effects on the expression of IκBα and extracellular signal‐regulated kinases 1/2 (ERK1/2). These effects might be achieved through regulating the AGEs‐RAGE‐IκBα‐ERK1/2 signaling pathway, among which, ERK1/2 might be the key protein. The study provides direct preclinical evidence for the research of Cornuside, which may become an excellent candidate drug for the treatment of aging‐related AD.

BACKGROUND:The extension of average life expectancy and the aggravation of population aging have become the inevitable trend of human development. In an aging society, various problems related to medical care for the elderly have become increasingly prominent. However, most of the age-related diseases have the characteristics of multiple diseases at the same time, prone to complications, and atypical clinical manifestations, which bring great difficulties to its treatment. Galangin (3,5,7-trihydroxyflavone) is a natural active compound extracted from the root of Alpinia officinarum Hance (Zingiberaceae). Recently, many studies have shown that galangin has potential advantages in the treatment of neurodegenerative diseases and cardiovascular and cerebrovascular diseases, which are common in the elderly. In addition, it also showed that galangin had prospective activities in the treatment of tumor, diabetes, liver injury, asthma and arthritis.PURPOSE:This review aims to systematically summarize and discuss the effects and the underlying mechanism of galangin in the treatment of age-related diseases.METHODS:We searched PubMed, SciFinder, Web of Science and CNKI literature database resources, combined with the keywords "galangin", "neurodegenerative disease", "tumor", "diabetes", "pharmacological activity", "drug combination", "pharmacokinetics", "drug delivery system" and "safety", and comprehensively reviewed the pharmacological activities and mechanism of galangin in treating age-related diseases.RESULTS:According to the previous studies on galangin, the anti-neurodegenerative activity, cardiovascular and cerebrovascular protective activity, anti-tumor activity, anti-diabetes activity, anti-arthritis activity, hepatoprotective activity and antiasthmatic activity of galangin were discussed, and the related mechanisms were classified and summarized in detail. In addition, the drug combination, pharmacokinetics, drug delivery system and safety of galangin were furtherly discussed.CONCLUSIONS:This review will provide reference for galangin in the treatment of age-related diseases. Meanwhile, further experimental research and long-term clinical trials are needed to determine the therapeutic safety and efficacy of galangin.

BACKGROUND AND PURPOSE Sigma-1 receptor (Sigma-1R), a chaperone protein with the ability to activate brain-derived neurotrophic factor (BDNF) signaling, has been connected with antidepressant action. Our previous study indicated that loganin has antidepressant-like effects. This study aimed to investigate whether loganin exerts antidepressant-like effects via Sigma-1R/BDNF signaling. EXPERIMENTAL APPROACH We established rat model of depression using chronic unpredictable stress (CUS). Sucrose preference test (SPT) and open field test (OFT) were used to evaluate the antidepressant-like effects of loganin. Then, we assessed the changes of BDNF signaling, synaptic plasticity and neurogenesis in hippocampus using western blot and immunohistochemical analysis. To confirm the role of Sigma-1R and BDNF in loganin-induced antidepressant-like effects, BD1047 and ANA-12 were used to block Sigma-1R and BDNF, respectively. KEY RESULTS Loganin improved depressive-like behaviors of rats in the SPT and OFT. Antidepressant-like effects of loganin in the SPT occur at day 6, which was faster than fluoxetine. Mechanismly, loganin effectively restored CUS-induced decrease in BDNF, pERK/1/2, PSD-95 and DCX in the hippocampus. Blockage of BDNF signaling with ANA-12 reversed the antidepressant-like effects of loganin. Moreover, loganin exhibited a binding affinity with Sigma-1R, as indicated by molecular docking. Importantly, BD1047 diminished loganin-induced improvement of rat behaviors as well as activation of hippocampal BDNF signaling. CONCLUSIONS AND IMPLICATIONS In conclusion, loganin exerts antidepressant-like effects by improving synaptic plasticity and neurogenesis in the hippocampus dependent on Sigma-1R/BDNF signaling.

目的:通过比较处方前置审核系统实施前后该院中心药房口服药超量医嘱情况,探讨处方前置审核系统在医院处方质量管理中的作用,促进临床合理用药.方法:抽取2017年10月17日至2018年10月16日(处方前置审核系统实施前)和2018年10月17日至2021年9月16日(处方前置审核系统实施后)该院中心药房口服药超量医嘱,进行回顾性分析.结果:处方前置审核系统实施前,该院中心药房口服药超量医嘱涉及的药物主要为心血管系统用药(20.0％,650条/3245条),口服药超量医嘱分布最多的科室为呼吸与危重症医学科(23.6％,766条/3245条).处方前置审核系统实施后,该院中心药房口服药超量医嘱的发生率降低,由实施前的20.0％(3245条/16201条)降至7.7％(2424条/31630条).结论:该院口服药超量医嘱涉及品种多,科室分布范围广,超量医嘱的发生比较常见.为了规范医嘱用量,对于超量医嘱所占比例较高的品种,应用处方前置审核系统设定规则进行拦截,可明显改善超量医嘱的发生以及临床不合理用药现状,提高住院患者口服药医嘱的质量,促进合理用药.同时,建议医院坚持建立本院的自主维护知识库,对药品进行精细化设置,既能阻止不合理处方/医嘱的开具,又能根据信息提示为患者用药个体化提供依据.

Iridoid glycosides (IGs) are found in many medicinal and edible plants, such as Gardenia jasminoides, Cistanche tubulosa, Eucommia ulmoides, Rehmanniae Radix, Lonicera japonica, and Cornus officinalis. Loganin, an IG, is one of the main active ingredient of Cornus officinalis Sieb. et Zucc., which approved as a medicinal and edible plant in China. Loganin has been widely concerned due to its extensive pharmacological effects, including anti-diabetic, antiinflammatory, neuroprotective, and anti-tumor activities, etc. Studies have shown that these underlying mechanisms include anti-oxidation, antiinflammation and anti-apoptosis by regulating a variety of signaling pathways, such as STAT3/NF-κB, JAK/STAT3, TLR4/NF-κB, PI3K/Akt, MCP-1/CCR2, and RAGE/Nox4/p65 NF-κB signaling pathways. In order to better understand the research status of loganin and promote its application in human health, this paper systematically summarized the phytochemistry, analysis methods, synthesis, pharmacological properties and related mechanisms, and pharmacokinetics based on the research in the past decades.

Though a great many of studies on the development of antidepressants for the therapy of major depression disorder (MDD) and the development of antidepressants have been carried out, there still lacks an efficient approach in clinical practice. The involvement of Sigma-1 receptor in the pathological process of MDD has been verified. In this review, recent research focusing on the role of Sigma-1 receptor in the etiology of MDD were summarized. Preclinical studies and clinical trials have found that stress induce the variation of Sigma-1 receptor in the blood, brain and heart. Dysfunction and absence of Sigma-1 receptor result in depressive-like behaviors in rodent animals. Agonists of Sigma-1 receptor show not only antidepressant-like activities but also therapeutical effects in complications of depression. The mechanisms underlying antidepressant-like effects of Sigma-1 receptor may include suppressing neuroinflammation, regulating neurotransmitters, ameliorating brain-derived neurotrophic factor and N-Methyl-D-Aspartate receptor, and alleviating the endoplasmic reticulum stress and mitochondria damage during stress. Therefore, Sigma-1 receptor represents a potential target for antidepressants development.

Ethnopharmacological relevance: Cornus officinalis Sieb. et Zucc., traditional Chinese medicine, has been widely used in the treatment of dementia. Cornel iridoid glycosides of Cornus officinalis is therapeutic to Alzheimer's disease (AD), while its pharmacodynamic material basis is not clear. Cornuside, an iridoid glycoside extracted from of Cornus officinalis Sieb. et Zucc, might be a potential anti-AD candidate.Aim of the study: Cornuside was evaluated for its effect on scopolamine induced AD mice, and its action mechanisms were explored.Materials and methods: ICR mice were administered with 1 mg/kg scopolamine intraperitoneally to induce amnesia. The therapeutic effect of cornuside of cognitive function was evaluated via series of behavioral tests, including Morris water maze test, step-through test and step-down test. In addition, specific enzyme reaction tests were used to detect the content of acetylcholine (ACh) and malondialdehyde (MDA), as well as the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), catalase (CAT), monoamine oxidase (MAO) in the brain. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). Results: Cornuside ameliorated the spatial memory impairment in Morris water maze test and cognitive disruption in step-through and step-down test. Furthermore, cornuside improved the level of ACh by reducing the activities of AChE and BuChE, and increasing the activity of ChAT in hippocampus. Cornuside also increased the levels of monoamine neurotransmitters by inhibiting MAO activity in hippocampus and cortex. In addition, cornuside attenuated MDA by enhancing the activities of SOD and CAT in hippocampus and cortex. Conclusion: Cornuside improved cognitive dysfunction induced by scopolamine in behavioral tests. The mechanisms of cornuside were further investigated from the aspects of neurotransmitters and oxidative stress. Cornuside could inhibit oxidative stress and neurotransmitter hydrolases, increase ACh and monoamine neurotransmitters, which finally contributed to its therapeutic effect on scopolamine induced amnesia.

Jolkinolide B is a typical ent-abietane-type diterpenoid, which is first found in Euphorbia jolkini. It is one of the most important active components in many toxic Euphorbia plants. In recent years, jolkinolide B has garnered increasing attention due to its high potent and multiple pharmacological activities. In order to better understand the research status of jolkinolide B, relevant information about jolkinolide B was collected from scientific databases (SciFinder Scholar, PubMed, ACS website, Elsevier, Web of Science, Google Scholar, Science Direct, and CNKI). There are few studies on chemical synthesis and biosynthesis of jolkinolide B. In addition, researchers on the activities of jolkinolide B are mostly concentrated at the cellular level, and there is a lack of research on the mechanism. In this review, the possible applications of jolkinolide B were systematically illustrated for the first time, from plant sources, physicochemical properties, analytical methods, synthesis and pharmacological activities. Jolkinolide B exhibits extensive pharmacological properties, including anticancer, anti-inflammatory, anti-osteoporosis, and anti-tuberculosis activities. Pharmacological activities of jolkinolide B were mainly focused on anticancer and anti-inflammatory activities, and the mechanism of action may be related with inhibition of JAK/STAT pathway, NF-κB pathway and PI3K/Akt/mTOR pathway. In addition, the extraction methods and analytical methods discussed in this review, will facilitate the development of novel herbal products for better healthcare solutions.

The genus Datura has been used as an important traditional medicine in China, as well as in other countries worldwide. This review summarizes the latest progress and perspective of the genus Datura, from the aspects of botany, traditional uses, phytochemistry, pharmacology, and toxicology. Up to May 2022, literatures were collected from online scientific databases, including Google Scholar, PubMed, SciFinder, CNKI, ACS, and Web of Science, and information was also obtained from “Flora Republicae Populairs Sinicae”, Chinese Pharmacopoeia, Chinese herbal classic books, and Ph.D. and M. Sc. dissertations. Studies on chemical constituents, pharmacological activities, and toxicity are mainly focused on D. metel, D. stramonium, and D. inoxia. Furthermore, 496 compounds have been discovered from the genus Datura, including withanolides, alkaloids, flavonoids, terpenoids, phenylpropanoids, steroids, amino acids, aromatics, and aliphatics. Among them, withanolides and alkaloids are two main active constituents. Pharmacological activities of extracts and compounds have been studied from the aspects of antitumor, antiinflammation, antioxidant, antimicrobial, antispasmodic, anticoagulant, analgesic, hypoglycemic and xanthine oxidase inhibitory activities, as well as the effects on central nervous system and immune system. Modern pharmacological studies have provided more clues to elucidate the traditional usages. The toxicity of the genus Datura is noteworthy, especially the potential toxicity on organs. This review would provide a comprehensive and constructive overview for new drug development and utilization of the genus Datura.

The genus Stellera Linn. consists of species of perennial herbs and shrubs, and is mainly distributed in the temperate regions of east Asia to west Asia. There are 10∼12 species in the world, two species in China: Stellera chamaejasme Linn. and Stellera formosana Hayata ex Li. As recorded, the roots of Stellera species are used to dissipate phlegm and relieve pain. The roots and the barks can be used for papermaking.This review aims to summarize the ethnopharmacological uses, chemical constituents, pharmacological activities, clinical applications and toxicology of the genus Stellera to better understand their therapeutic potential in the future.The relevant information of the genus Stellera was collected from scientific databases (Pubmed, ACS website, SciFinder Scholar, Elsevier, Google Scholar, Web of Science and CNKI). Information was also gathered from 'Flora Republicae Popularis Sinicae (〈〈〉〉)', folk records, conference papers on ethnopharmacology, Ph.D. and Masters' Dissertation.Stellera plants have been studied as traditional folk medicines all around the world. The chemical constituents of Stellera species mainly comprise terpenoids, flavonoids, coumarins, lignans, and so on. Extracts and compounds of Stellera species exhibit extensive pharmacological activities, such as anti-tumor, anti-viral, anti-convulsive, anti-epileptic, anti-bacterial and anti-insect activities, etc. Clinical applications have suggested that the genus Stellera has the effects in treating several skin diseases and cancers, however, the results should be further verification. The genus Stellera plants are toxic and should be used reasonable.This paper reviewed the ethnopharmacological uses, chemical constituents, pharmacology, clinical applications and toxicology of the genus Stellera. The genus Stellera has broad application prospects. However, further in-depth studies are needed to determine the medical uses of the genus and its chemical constituents, pharmacological activities, clinical applications and toxicology.

Euphorbia ebracteolata Hayata, as a traditional medicine, is widely distributed in China, Korea and Japan. In China, the dried root of this plant is named 'langdu'. It is traditionally used to treat oedema, skin ulcers, abdominal distension, cough, asthma, tuberculosis swelling and other diseases. Previous studies have found that the chemical constituents of E. ebracteolata are mainly concentrated in terpenoids, acetophenones, and flavonoids. Both extracts and pure compounds from E. ebracteolata were found to possess many pharmacological activities, such as anticancer, anti-inflammatory, antiviral, and antimicrobial effects. In addition, it was reported that E. ebracteolata shows toxicity. To provide inspiration for further in-depth studies on this plant, this review will provide a timely and systematic summary of E. ebracteolata in traditional uses, phytochemistry, pharmacology toxicology, and quality control.

A series of 4-thiazolinone derivatives (D1-D58) were designed and synthesized. All of the derivatives were evaluated in vitro for neuraminidase (NA) inhibitory activities against influenza virus A (H1N1), and the inhibitory activities of the five most potent compounds were further evaluated on NA from two different influenza viral subtypes (H3N2 and B), and then their in vitro anti-viral activities were evaluated using the cytopathic effect (CPE) reduction assay. The results showed that the majority of the target compounds exhibited moderate to good NA inhibitory activity. Compound D18 presented the most potent inhibitory activity with IC50 values of 13.06 mu M against influenza H1N1 subtype. Among the selected compounds, D18 and D41 turned out to be the most potent inhibitors against influenza virus H3N2 subtype (IC50 = 15.00 mu M and IC50 = 14.97 mu M, respectively). D25 was the most potent compound against influenza B subtype (IC50 = 16.09 mu M). In addition, D41 showed low toxicity and greater potency than reference compounds Oseltamivir and Amantadine against N1-H275Y variant in cellular assays. The structure-activity relationship (SAR) analysis showed that introducing 4-CO2H, 4-OH, 3-OCH3-4-OH substituted benzyl methylene can greatly improve the activity of 4-thiazolinones. Further SAR analysis indicated that 4-thiazolinone and ferulic acid fragments are necessary fragments of target compounds for inhibiting NA. Molecular docking was performed to study the interaction between compound D41 and the active site of NA. This study may providing important information for new drug development for anti-influenza virus including mutant influenza virus. (C) 2021 Elsevier Masson SAS. All rights reserved.