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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®BEH C18 (2.1 × 50 mm, 1.7 μm) 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: 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., Aim of This Review: 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., Materials and Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Ginsenoside Rg1 (Rg1), one of the major bioactive ingredients of Panax ginseng C. A. Mey, has neuroprotective effects in animal models of depression, but the mechanism underlying these effects is still largely unknown AIM OF THE STUDY: Gap junction intercellular communication (GJIC) dysfunction is a potentially novel pathogenic mechanism for depression. Thus, we investigated that whether antidepressant-like effects of Rg1 were related to GJIC., Materials and Methods: Primary rat prefrontal cortical and hippocampal astrocytes cultures were treated with 50μM CORT for 24h to induce gap junction damage. Rg1 (0.1, 1, or 10μM) or fluoxetine (1μM) was added 1h prior to CORT treatment. A scrape loading and dye transfer assay was performed to identify the functional capacity of gap junctions. Western blot was used to detect the expression and phosphorylation of connexin43 (Cx43), the major component of gap junctions., Results: Treatment of primary astrocytes with CORT for 24h inhibited GJIC, decreased total Cx43 expression, and increased the phosphorylation of Cx43 at serine368 in a dose-dependent manner. Pre-treatment with 1μM and 10μM Rg1 significantly improved GJIC in CORT-treated astrocytes from the prefrontal cortex and hippocampus, respectively, and this was accompanied by upregulation of Cx43 expression and downregulation of Cx43 phosphorylation., Conclusion: These findings provide the first evidence indicating that Rg1 can alleviate CORT-induced gap junction dysfunction, which may have clinical significance in the treatment of depression., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)