Anti-inflammatory effects of Morus alba Linne bark on the activation of toll-like receptors and imiquimod-induced ear edema in mice.

BACKGROUND: Morus alba L. bark has been widely used in traditional medicine for treating several inflammatory diseases, such as hypertension, diabetes mellitus and coughing; however, the molecular mechanisms underlying its anti-inflammatory effects are not well understood. METHODS: We examined the effects of an extract of Morus alba L. bark (MabE) on Toll-like receptor (TLR) ligand-induced activation of RAW264.7 macrophages using a luciferase reporter assay and immunoassays. For the in vivo experiment, we used an imiquimod-induced ear edema model to examine the anti-inflammatory effects of MabE. RESULTS: MabE inhibited the TLR ligand-induced activation of NF-κB in RAW264.7 cells without affecting their viability. Consistent with the inhibition of NF-κB activation, MabE also inhibited the production of IL-6 and IL-1ß from TLR ligand-treated RAW264.7 cells. In vivo MabE treatment inhibited the ear swelling of IMQ-treated mice, in addition to the mRNA expression of IL-17A, IL-1ß and COX-2. The increases in splenic γδT cells in IMQ-treated mice and the production of IL-17A from splenocytes were significantly inhibited by MabE treatment. CONCLUSION: Our study suggests that the anti-inflammatory effects of MabE on the activation of the macrophage cell line RAW246.7 by TLRs and IMQ-induced ear edema are through the inhibition of NF-κB activation and IL-17A-producing γδT cells, respectively.

Anti-inflammatory activities of isopimara-8(14),-15-diene diterpenoids and mode of action of kaempulchraols P and Q from Kaempferia pulchra rhizomes.

Inflammation is an extensively recognized link to many pathological diseases. It is a host response for protection from infections and tissue damage. Infections trigger acute inflammation; however, persistent infection will contribute to chronic inflammation and higher disease susceptibility. Deregulated inflammatory responses can cause excessive or long-lasting tissue damage, manifested as cancer, immune disorders, diabetes, etc. NF-κB is a central mediator of pro-inflammatory gene induction and functions in both innate and adaptive immune cells; therefore, the anti-inflammatory regulation of NF-κB is needed. Natural products reportedly play an important role in controlling the inflammatory response pathways. However, the anti-inflammatory activities of isopimara-8-(14),15-diene diterpenoids have not yet been fully elucidated. To elucidate the anti-inflammatory activities of the isopimara-8(14),15-diene diterpenoids, we investigated 21 isopimara-8(14),15-diene diterpenoids previously isolated from Kaempferia pulchra rhizomes. Eleven compounds exhibited NO inhibitory activity against lipopolysaccharide (LPS)-induced RAW264.7 cells, with IC50 values ranging from 30 to 100 µM. Furthermore, the most potent kaempulchraols P and Q, with IC50 values of 39.88 and 36.05 µM, respectively, inhibited the NF-κB-mediated transactivation of a luciferase reporter gene, IL-6 production, and COX-2 expression, with an effective dose of 25 µM. These findings provide new insights into the anti-inflammatory activities of the isopimara-8(14),15-diene diterpenoids.

Relationship between KCNQ1 (LQT1) and KCNH2 (LQT2) gene mutations and sudden death during illegal drug use.

Long QT syndrome (LQTS), a congenital genetic disorder, can cause torsades de pointes (TdP), and lethal cardiac arrhythmia may result from ingestion of cardiotoxic drugs. Methamphetamine (MP) and new psychoactive substances (NPSs) can trigger TdP due to QT prolongation, leading to sudden death. We therefore analysed variations in the LQTS-associated genes KCNQ1 (LQT1) and KCNH2 (LQT2) using cardiac blood and myocardial tissue from subjects having died suddenly during MP or NPS use to investigate the relationship between congenital genetic abnormalities and sudden death during illegal drug use. We amplified and sequenced all exons of these genes using samples from 20 subjects, half of whom had died taking MP and half after using NPSs. G643S, a KCNQ1 missense polymorphism, was significantly more common among sudden deaths involving NPSs (6 subjects) than those involving MP (1 subject) and healthy Japanese subjects (P = 0.001). Notably, synthetic cathinones were detected in 2 of 3 cases involving G643S carriers. Previous functional analyses have indicated that the G643S polymorphism in the KCNQ1 potassium channel gene causes mild IKs channel dysfunction. Our data suggest that use of NPSs, particularly synthetic cathinones, is associated with elevated risk of serious cardiac arrhythmia and sudden death for subjects carrying KCNQ1 G643S.

Diagnosable and non-diagnosable causes of death by postmortem computed tomography: a review of 339 forensic cases.

Postmortem computed tomography (PMCT) is often used to diagnose causes of death, especially in nations with a low autopsy rate. To identify the causes of death that can and cannot be determined by PMCT, imaging findings were reviewed in 339 consecutive forensic autopsy cases. Causes of death could be determined based on PMCT findings alone in 7% of these cases, based on suggestive PMCT findings with additional information in 54%, and could not be determined by PMCT in 38%. PMCT screening may be useful for establishment of some causes of death, including traumatic intracranial hematoma, endogenous intracranial hemorrhage, and some cases of cardiac rupture. Suggestive findings from PMCT in other cases, such as those involving subarachnoid hemorrhage or pericardial hematoma, can lead to misdiagnosis and may be a pitfall of PMCT screening. Causes of death including some cases of cervical cord injuries, asphyxiation, burn, drug intoxication, acute myocardial infarction, and pulmonary thromboembolism cannot be diagnosed using PMCT.

Evaluation of computed tomography as a screening test for death inquest.

The Japanese method of inquest, which depends mostly on external examinations, may misdiagnose a considerable number of accidental deaths and suicides as death by disease. We conducted computed tomography (CT) scans of 80 cases for which police concluded death by disease or natural causes based on police investigations into the circumstances and results from external examinations. The cause of death was clearly determined by CT scan in 17 of 80 cases. Ten cases underwent autopsy after the police suspected criminality based on results of the CT examinations. The results suggest CT scan may be a tool for preventing a number of overlooked crimes and accidents in Japan. However, it cannot be a perfect tool for discerning between death by disease and other causes of death without cooperation from the investigative agencies and subsequent forensic examinations such as autopsy and toxicological tests.

Can cervical spine injury be correctly diagnosed by postmortem computed tomography?

We discuss the usefulness of postmortem computed tomography (PMCT) by reviewing cases of cervical spine injury. A merit of PMCT is that it can identify injury that cannot be found on autopsy; however, peculiar defects of it may exist. While PMCT can identify bone fractures, it cannot indicate whether the injury was inflicted while the deceased was still alive or not because of its inability to clearly image bleeding around the fracture. Furthermore, CT often misses some types of cervical spine injuries, such as laceration of an intervertebral disk and incomplete fracture of the cervical spine. On the other hand, cervical spine injury on CT images occasionally has an appearance similar to subarachnoid hemorrhage due to rupture of the cerebral artery, indicating that cervical spine injury can be misdiagnosed as a disease by PMCT. When PMCT is used for screening trauma, caution must be observed regarding its limitations. If the possibility of trauma of the neck or head is not completely ruled out from the personal history of the victim, autopsy is strongly recommended, even when PMCT findings indicate that the cause of death may be due to disease, such as subarachnoid hemorrhage.