Simultaneous Determination of Thirteen Iridoid Glycosides in Crude and Processed Fructus Corni from Different Areas by UPLC-MS/MS Method.

Fructus Corni (F. Corni) is the dried mature pulp of Cornus officinalis Sieb. et Zucc.(Cornaceae), which is rich in iridoids. In this study, a simple, sensitive and rapid UPLC-MS/MS method was developed for the simultaneous determination of 13 iridoid glycosides of F. Corni from different areas. Specifically, we included five new compounds (cornusdiridoid C, cornusdiridoid E, cornusdiridoid F, 3'',5''-dehydroxycornuside and 2'-O-p-coumaroyl-kingiside) and isomers (2'-O-p-E-coumaroylloganin and 2'-O-p-Z-coumaroylloganin) for the first time in the quality markers of F. Corni. A total of 13 compounds and two pairs of isomers were well isolated and tested within just 14 min. All calibration curves showed good linear regression (r2 ≥ 0.99) within the tested concentration ranges. The limit of detection and limit of quantification were in the range of 0.19-1.90 and 0.38-3.76 ng/mL, respectively. The intra-day and inter-day precision were <3.21% and 12.49%, the RSD values of repeatability did not exceed 6.81% and the average recoveries were 90.95-113.59% for the analytes. All iridoid glycosides stabilized within 12 h (RSD < 10.99%). This method has been successfully applied to the quality evaluation of crude and processed F. Corni from different areas. The determination of characteristic iridoid glycosides and isomers will provide a more reliable and comprehensive method for the evaluation of F. Corni.

Pharmacological activities and therapeutic potential of galangin, a promising natural flavone, in age-related diseases.

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.

Stelleratenoids A-F, macrocyclic daphnane orthoesters with anti-HIV activity from the roots of Stellera chamaejasme L.

Six undescribed macrocyclic daphnane orthoesters, stelleratenoids A-F (1-6), were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic analyses, including HRESIMS and NMR spectra. Compound 1 features an unusual terminal double bond at C-2/C-19 in the 1α-alkyldaphnane lactone skeleton. Compounds 2-4 are unique in the presence of different long chain fatty acyl groups. Compounds 5 and 6 are unique examples of modified macrocyclic daphnane diterpenoids. All the isolates were evaluated for anti-HIV activity in MT-2 cells. Among them, compounds 1, 5 and 6 exhibited highly potent anti-HIV activity with EC50 values of 66.70, 10.62 and 55.10 nM, respectively, possessing high potential to develop new anti-HIV drugs.

New Rosane Diterpenoids and Their Analogs from Euphorbia ebracteolata Hayata.

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.

Loganin improves chronic unpredictable mild stress-induced depressive-like behaviors and neurochemical dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc., is a valuable herb commonly used in Chinese medicine clinics. Loganin is a major iridoid glycoside obtained from the traditional Chinese herb Corni Fructus. Loganin, which has been shown to improve depression-like behavior in mice exposed to acute stress, is probably a potential antidepressant candidate. AIM OF THE STUDY: Loganin was evaluated for its effect on chronic unpredictable mild stress (CUMS) induced depressive-like mice, and its action mechanisms were explored. MATERIALS AND METHODS: ICR mice were subjected to the CUMS stimulation method to induce depression. The therapeutic effect of loganin on depressive-like behavior was evaluated by a series of behavioral tests such as sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST) and open-field test (OFT). In addition, the serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using ELISA. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were measured using western blot analysis. RESULTS: The results showed that CUMS induced depressive-like behaviors in mice, as indicated by behavioral tests. Administration of loganin increased the sucrose preference in SPT, as well as decreased the immobility time in FST and TST. Loganin could also improve food intake, and increased crossing times in the OFT. In mechanism, loganin restored the secretion of monoamine neurotransmitters, ACTH and CORT to normal levels. In addition, loganin elevated the expression of BDNF in the hippocampus. In conclusion, loganin exerts antidepressant-like effects in CUMS model mice through modulating monoamine neurotransmitters, ACTH, CORT and BDNF. CONCLUSION: Loganin effectively ameliorated depressive-like symptoms in CUMS-exposed mice by increasing 5-hydroxytryptamine (5-HT) and dopamine (DA) levels, alleviating hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and increasing BDNF expression. In conclusion, the findings of the current study extensive evidence for the application of loganin in stress-associated disorders, specifically targeting depression.

Hypericin: A natural anthraquinone as promising therapeutic agent.

BACKGROUND: Hypericin is a prominent secondary metabolite mainly existing in genus Hypericum. It has become a research focus for a quiet long time owing to its extensively pharmacological activities especially the anti-cancer, anti-bacterial, anti-viral and neuroprotective effects. This review concentrated on summarizing and analyzing the existing studies of hypericin in a comprehensive perspective. METHODS: The literature with desired information about hypericin published after 2010 was gained from electronic databases including PubMed, SciFinder, Science Direct, Web of Science, China National Knowledge Infrastructure databases and Wan Fang DATA. RESULTS: According to extensive preclinical and clinical studies conducted on the hypericin, an organized and comprehensive summary of the natural and artificial sources, strategies for improving the bioactivities, pharmacological activities, drug combination of hypericin was presented to explore the future therapeutic potential of this active compound. CONCLUSIONS: Overall, this review offered a theoretical guidance for the follow-up research of hypericin. However, the pharmacological mechanisms, pharmacokinetics and structure activity relationship of hypericin should be further studied in future research.

Hyperforin: A natural lead compound with multiple pharmacological activities.

Hypericum perforatum L. (Clusiaceae), commonly known as St. John's wort, has a rich historical background as one of the oldest and most widely studied herbal medicines. Hyperforin is the main antidepressant active ingredient of St. John's wort. In recent years, hyperforin has attached increasing attention due to its multiple pharmacological activities. In this review, the information on hyperforin was systematically summarized. Hyperforin is considered to be a lead compound with diverse pharmacological activities including anti-depression, anti-tumor, anti-dementia, anti-diabetes and others. It can be obtained by extraction and synthesis. Further pharmacological studies and more precise detection methods will help develop a value for hyperforin. In addition, structural modification and pharmaceutical preparation technology will be beneficial to promoting the research progress of hyperforin based innovative drugs. Although these works are full of known and unknown challenges, researchers are still expected to make hyperforin play a greater value.

The NLRP3 inflammasome in depression: Potential mechanisms and therapies.

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.

Jolkinolide B: A comprehensive review of its physicochemical properties, analytical methods, synthesis and pharmacological activity.

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.

Cornuside Is a Potential Agent against Alzheimer's Disease via Orchestration of Reactive Astrocytes.

Cornuside is an iridoid glycoside from Cornus officinalis, with the activities of anti-inflammatory, antioxidant, anti-mitochondrial dysfunction, and neuroprotection. In the present research, a triple-transgenic mice model of AD (3 × Tg-AD) was used to explore the beneficial actions and potential mechanism of cornuside on the memory deficits. We found that cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway. We further confirmed that LY294002 and Nrf2 silencing could block the cornuside-mediated phenotypic switch of C6 cells induced by microglia conditioned medium (MCM) in response to lipopolysaccharide (LPS), which indicated that the effects of cornuside in astrocyte activation are dependent on AKT/Nrf2/NF-κB signaling. In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.

Sigma-1 receptor: A potential target for the development of antidepressants.

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.

Diverse gallotannins with α-glucosidase and α-amylase inhibitory activity from the roots of Euphorbia fischeriana steud.

A phytochemical investigation of the roots of Euphorbia fischeriana Steud. led to the isolation of eleven undescribed gallotannins, fishertannins A-K, together with four known analogues. Their structures were elucidated by the comprehensive spectroscopic data including UV, IR, HR-ESI-MS, and NMR, while the absolute configurations of the sugar moiety were determined by the acid hydrolysis and HPLC analyses. Fishertannin A possessed an unusual skeleton comprised of acetophenone, galloyl group, arabinofuranosyl and glucopyranosyl moieties. Fishertannin B, fishertannin H, fishertannin K, 1,2,3-tri-O-galloyl-ß-D-glucopyranose, 3,4,6-tri-O-galloyl-D-glucopyranose, and 1,6-di-O-galloyl-ß-D-glucopyranose displayed the potent α-glucosidase inhibitory activities with the IC50 values of 15.48-177.13 µM. Examination of the structure-activity relationships (SAR) demonstrated that the galloyl and glucopyranosyl moieties played a key role in the inhibitory activity for both α-glucosidase and α-amylase inhibitory activity. Among all isolates, 1,2,3-tri-O-galloyl-ß-D-glucopyranose showed the most potent and highly specific inhibitory activity against α-glucosidase with an IC50 value of 15.48 ± 0.60 µM. The kinetic analysis of 1,2,3-tri-O-galloyl-ß-D-glucopyranose disclosed the mixed inhibition type on α-glucosidase, and the molecular docking visualized the stable binding with the catalytic pocket of α-glucosidase (pdb 3A4A). These findings indicated the excellent antidiabetic potential of the gallotannins from E. fischeriana, while 1,2,3-tri-O-galloyl-ß-D-glucopyranose could be developed as a promising candidate for the treatment of T2DM with fewer side effects.

The untapped potential of spermidine alkaloids: Sources, structures, bioactivities and syntheses.

Spermidine alkaloids are a kind of natural products possessing an aliphatic triamine structure with three or four methylene groups between two N-atoms. Spermidine alkaloids exist in plants, microorganisms, and marine organisms, which usually form amide structures with cinnamic acid or fatty acid derivatives. Their unique structures showed a wide range of biological activities such as neuroprotective, anti-aging, anti-cancer, antioxidant, anti-inflammatory, and antimicrobial. In order to better understand the research status of spermidine alkaloids and promote their applications in human health, this paper systematically reviewed the biological sources, structures, pharmacological actions, and synthetic processes of spermidine alkaloids over the past two decades. This will help to open up new pharmacological investigation fields and better drug design based on these spermidine alkaloids.

Concurrent severe pulmonary tuberculosis with Evans syndrome: a case report with literature review.

BACKGROUND: Tuberculosis is a bacterial infection involving multiple organs and systems. Its hematological presentation mainly includes anemia and leukocytosis. Evans syndrome is a rare autoimmune disease characterized by autoimmune hemolytic anemia, immune thrombocytopenia, and neutropenia, with positive results for the direct Coombs test and platelet antibodies. The cooccurrence of tuberculosis and Evans syndrome is rarely reported. CASE PRESENTATION: A 69-year-old female presented with a fever and shortness of breath. Her chest computerized tomography scan showed extensive miliary nodules in the bilateral lung fields. She rapidly developed respiratory failure that required endotracheal intubation and mechanical ventilation. The acid-fast bacilli sputum smear results indicated a grade of 3+. Later on, blood testing revealed hemolytic anemia, a positive direct Coombs test result, and the presence of the platelet antibody IgG. This patient was diagnosed as having disseminated pulmonary tuberculosis and Evans syndrome. She successfully recovered after treatment with antituberculosis drugs and glucocorticoids. CONCLUSIONS: Tuberculosis can occur together with Evans syndrome. Affected patients should receive both antituberculosis and immunosuppressive drugs.

Phytochemistry, synthesis, analytical methods, pharmacological activity, and pharmacokinetics of loganin: A comprehensive review.

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.

Cornuside ameliorates cognitive impairments in scopolamine induced AD mice: Involvement of neurotransmitter and oxidative stress.

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.

The Correlation between 25-Hydroxyvitamin D3 and the Severity and Short-Term Prognosis of Pulmonary Tuberculosis.

BACKGROUND: Pulmonary tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis in the lungs. The present study aims to investigate the correlation between serum 25-hydroxyvitamin D3 (25-VD3) and the severity and short-term prognosis of tuberculosis. METHODS: The clinical data of 261 pulmonary tuberculosis patients, who were admitted to the Tuberculosis Diagnosis and Treatment Center of our hospital from January 1, 2017 to December 31, 2020, was retrospectively collected. Taking the median of 25-VD3 at admission (11.40 ng/mL) as the cutoff value, these patients were divided into two groups: high 25-VD3 group (> 11.40 ng/mL, n = 131) and low 25-VD3 group (≤ 11.40 ng/mL, n = 130). Then, Pearson's correlation analysis was performed using SPSS to determine the correlation between the 25-VD3 level and the length of hospitalization and Acute Physiology and Chronic Health Evaluation II (APACHE II) score of pulmonary tuberculosis patients. According to the clinical outcome after 28 days of treatment, these patients were divided again into two groups: improvement group (n = 170) and death group (n = 91). Then, Pearson's correlation analysis through SPSS was performed to determine the relationship between the 25-VD3 level and short-term prognosis of pulmonary tuberculosis patients. RESULTS: Compared to the low 25-VD3 group, pulmonary tuberculosis patients in the high 25-VD3 group were younger, had a higher percentage of improvement after 28 days of treatment, and had a lower APACHE II score (p < 0.05). However, the 25-VD3 level was not significantly correlated to the length of hospital stay of pulmonary tuberculosis patients (correlation coefficient r = 0.020, p = 0.746) and was significantly negatively correlated to the APACHE II score (correlation coefficient r = -0.211, p = 0.001). In addition, the age and APACHE II score of patients were lower in the improvement group, when compared to the death group, while the 25-VD3 level was higher and the length of hospital stay was longer, when compared to the death group (p < 0.01). The logistic regression analysis revealed that the length of hospital stay, APACHE II score, and 25-VD3 level are independent risk factors that affect the prognosis of pulmonary tuberculosis patients (p < 0.05). CONCLUSIONS: In summary, 25-VD3 is closely correlated to the severity of tuberculosis, and this can be used to evaluate and predict the prognosis of patients.

Jolkinolide B alleviates renal fibrosis via anti-inflammation and inhibition of epithelial-mesenchymal transition in unilateral ureteral obstruction mice.

Renal fibrosis is a critical pathological process lead to a progressive loss of renal function. Jolkinolide B (JB) is a natural compound with anti-inflammatory activity from Euphorbia fischeriana Steud. The study evaluated the effect of JB on renal fibrosis in mice with unilateral ureteral obstruction (UUO). The results showed that JB could decrease renal fibrotic area, reduce phosphorylation of NF-κB p65 and the release of TNF-α, IL-6 and IL-1ß, restore the expression of vementin, α-SMA and E-cadherin, as well as TGF-ß1 and p-smad2/3. In conclusion, JB might reduce renal fibrosis by inhibiting inflammation induced by NF-κB pathway and EMT mediated by TGF-ß1/Smad pathway.

Secoiridoid dimers and their biogenetic precursors from the fruits of Cornus officinalis with potential therapeutic effects on type 2 diabetes.

Cornusdiridoid A-F (1-6), six unusual cornuside-morroniside secoiridoid dimers, and their possible new biogenetic precursor, 3″,5″-dehydroxycornuside (7), together with four known secoiridoids (8-11), were obtained from the fruits of Cornus officinalis. Their structures were elucidated on the basis of various spectroscopic and chemical methods. A plausible biosynthetic pathway of compounds 1-11 was proposed. The α-glucosidase inhibitory, antioxidant and anti-inflammatory activities of these isolates were evaluated. Some of them emerged out as potent antidiabetic, anti-inflammatory and free radical scavenging agents. Molecular docking was also carried out for antidiabetic target α-glucosidase to investigate the possible binding modes of the most potent α-glucosidase inhibitor, vincosamide (9). These results revealed that the secoiridoids from C. officinalis fruits may be served as new potential antidiabetic agents to prevent and treat type 2 diabetes.

Identifying the mechanism underlying antidepressant-like effects of loganin by network pharmacology in combination with experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Loganin, an iridoid glycoside, is one of the quality control indexes of Cornus officinalis Sieb. et Zucc. Increasing evidence emphasize the important role of inflammation in the pathology of depression, which links depression with other chronic diseases. Loganin prevents inflammatory response in multiple diseases and reverses depressive-like behaviors. However, the mechanisms underlying antidepressant-like effects of loganin for the treatment of inflammation-associated depression are not utterly understood. AIM OF THE STUDY: The present study was designed to predict the potential targets of loganin against inflammation-associated depression using a network pharmacology approach. MATERIALS AND METHODS: Pharmmapper and Uniport were used to predict loganin-related targets. Targets of inflammation were identified through GeneCards databases and Online Mendelian Inheritance in Man (OMIM). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to identify the potential mechanism. Finally, qRT-PCR and ELISA were used to confirm the role of loganin on these targets. RESULTS: There were 15 nodes in the loganin-inflammation-depression intersection targets network. In the network, the degree value of CTNNB1 was above 3. Among top ten pathways identified by KEGG analysis, Th1/Th2 cell differentiation and IL-17 signaling pathways were related with both inflammation and depression. As indicated by qRT-PCR results, loganin increased CTNNB1 mRNA level. Moreover, loganin elevated M2 markers of microglia but decreased M1 markers of microglia against lipopolysaccharide (LPS), indicated by qRT-PCR results and ELISA results. CONCLUSION: CTNNB1 was the main target of loganin. Loganin alleviated LPS-induced inflammation through inhibiting M1 polarization of microglia. Our results provide a better understanding of loganin-induced antidepressant-like effects for the treatment of inflammation-associated depression.