Therapeutic potential of plant iridoids in depression: a review.

CONTEXT: Depression is a mental disorder characterized by low mood, reduced interest, impaired cognitive function, and vegetative symptoms such as sleep disturbances or poor appetite. Iridoids are the active constituents in several Chinese classical antidepressant formulae such as Yueju Pill, Zhi-Zi-Hou-Po Decoction, Zhi-Zi-Chi Decoction, and Baihe Dihuang Decoction. Parallel to their wide usages, iridoids are considered potential lead compounds for the treatment of neurological diseases. OBJECTIVE: The review summarizes the therapeutic potential and molecular mechanisms of iridoids in the prevention or treatment of depression and contributes to identifying research gaps in iridoids as potential antidepressant medication. METHODS: The following key phrases were sought in PubMed, Google Scholar, Web of Science, and China National Knowledge Internet (CNKI) without time limitation to search all relevant articles with in vivo or in vitro experimental studies as comprehensively as possible: ('iridoid' or 'seciridoid' or 'depression'). This review extracted the experimental data on the therapeutic potential and molecular mechanism of plant-derived iridoids for depression. RESULTS: Plant iridoids (i.e., catalpol, geniposide, loganin), and secoiridoids (i.e., morroniside, gentiopicroside, oleuropein, swertiamarin), all showed significant improvement effects on depression. DISCUSSION AND CONCLUSIONS: Iridoids exert antidepressant effects by elevating monoamine neurotransmitters, reducing pro-inflammatory factors, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, increasing brain-derived neurotrophic factor (BDNF) and its receptors, and elevating intestinal microbial abundance. Further detailed studies on the pharmacokinetics, bioavailability, and key molecular targets of iridoids are also required in future research, ultimately to provide improvements to current antidepressant medications.

Role of spinal RIP3 in inflammatory pain and electroacupuncture-mediated analgesic effect in mice.

AIMS: Electroacupuncture (EA) is a potentially useful treatment for inflammatory pain. Receptor-interacting protein 3 (RIP3) triggers the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome; activation independent of necroptosis has been reported. However, the role of RIP3 in inflammatory pain and its EA-induced analgesic effects remains unclear. MAIN METHODS: Mice were treated with EA (2 Hz, 2 mA) after complete Freund's adjuvant (CFA) pain models were established. Inhibition or activation of spinal RIP3 was achieved by intrathecal administration of GSK-843 (a specific RIP3 inhibitor) or microinjection of lentivirus-RIP3, respectively. Mechanical analgesiometry and thermal analgesiometry were used to assess paw withdrawal threshold and paw withdrawal latency in mice. Quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to evaluate the expression of RIP3 and NLPR3 in spinal dorsal horn (SDH) of mice. KEY FINDINGS: The expression of spinal RIP3 and NLPR3 increased significantly after CFA injection. Both intrathecal administration of GSK-843 and EA alleviated mechanical and thermal pain behaviors induced by CFA and inhibited the expression of RIP3 and NLRP3 in the SDH of CFA mice. Over-expression of RIP3 induces pain-like symptoms in mice and inhibits the regulatory effects of EA on inflammatory pain. SIGNIFICANCE: Our results indicate that the EA analgesia effect may be related to suppression of RIP3 and NLRP3 expression in the SDH. This study could provide potential insights into the underlying spinal mechanisms involved in the analgesic effect of EA.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients

BKCa channel is a molecular target of vitamin C to protect against ischemic brain stroke.

Epidemiological studies have demonstrated that vitamin C decreases the risk of stroke, which has generally been ascribed to its function as antioxidant and free radical scavenger. However, whether there is a defined molecular target for vitamin C on stroke is unknown. Utilizing middle cerebral artery occlusion (MCAO) in rats as a model for ischemic stroke, we demonstrated that long-term, low-dose administration of vitamin C prior to MCAO could exert significant neuroprotective effect on the brain damage. The long-term, low-dose vitamin C pretreated rats had decreased brain infarct size and decreased neurological deficit score compared with the vehicle or single high dose pretreated MCAO rats. Furthermore, electrophysiological experiments using patch clamp technique showed that vitamin C increased the whole-cell current of the large-conductance Ca2+-activated K+ (BKCa) channel. Moreover, vitamin C increased the open probability of the channel without change its amplitude. Importantly, blockade of the BKCa channels abolished the neuroprotective effect of vitamin C on MCAO. Therefore, this study shows that long-term, low-dose pretreatment with vitamin C could reduce MCAO-induced brain damage through activation of the BKCa channels, suggesting that the BKCa channel is a molecular target of vitamin C on stroke.