Vasorelaxant and Blood Pressure-Lowering Effects of Cnidium monnieri Fruit Ethanol Extract in Sprague Dawley and Spontaneously Hypertensive Rats.

Cnidium monnieri (L.) Cusson, a member of the Apiaceae family, is rich in coumarins, such as imperatorin and osthole. Cnidium monnieri fruit (CM) has a broad range of therapeutic potential that can be used in anti-bacterial, anti-cancer, and sexual dysfunction treatments. However, its efficacy in lowering blood pressure through vasodilation remains unknown. This study aimed to assess the potential therapeutic effect of CM 50% ethanol extract (CME) on hypertension and the mechanism of its vasorelaxant effect. CME (1-30 µg/mL) showed a concentration-dependent vasorelaxation on constricted aortic rings in Sprague Dawley rats induced by phenylephrine via an endothelium-independent mechanism. The vasorelaxant effect of CME was inhibited by blockers of voltage-dependent and Ca2+-activated K+ channels. Additionally, CME inhibited the vascular contraction induced by angiotensin II and CaCl2. The main active compounds of CM, i.e., imperatorin (3-300 µM) and osthole (1-100 µM), showed a concentration-dependent vasorelaxation effect, with half-maximal effective concentration values of 9.14 ± 0.06 and 5.98 ± 0.06 µM, respectively. Orally administered CME significantly reduced the blood pressure of spontaneously hypertensive rats. Our research shows that CME is a promising treatment option for hypertension. However, further studies are required to fully elucidate its therapeutic potential.

Anti-colitic effects of the modified Bojanggunbi-tang on dextran sulfate sodium-induced mouse colitis model.

Bojanggunbi-tang (BGT) is a well-known and widely used herbal prescription in Korea for colon diseases, with well-documented pharmacological effects on the digestive system. The current study aimed to develop a new simple and effective prescription using the original prescription. mBGT, a modified BGT, was developed by mixing the extracts of Lonicera japonica Thunb., Alisma orientalis and Atractylodes macrocephala based on a literature review and screening of 16 kinds of component herbs of BGT. A colitis mouse (Male, BALB/c) model was induced using dextran sulfate sodium (5%). The effects of BGT and mBGT on body weight, histological damage, clinical score, macroscopic score and colon length were compared. The mechanisms of action were analyzed based on cytokine production in colon tissue. mBGT at 300mg/kg showed similar effectiveness to that of BGT on colon shortening (P<0.01), clinical score (P<0.05), macroscopic score (P<0.01) and histological damage (P<0.01). In addition, mBGT decreased cytokines, including Interleukin 1 beta, tumor necrosis factor alpha and Interleukin 17, in a dose-dependent manner. In conclusion, mBGT could be a substitute prescription for BGT in clinics and a candidate for the development of a new BGT-based therapeutic agent against colitis.

Icariin Improves Functional Behavior in a Mouse Model of Traumatic Brain Injury and Promotes Synaptic Plasticity Markers.

Epimedii Herba (EH) has been used in traditional Asian medicine to treat hemiplegia following stroke. Icariin, its major active component, is used as a quality-control marker and for its various pharmacological effects. We hypothesized that icariin would show protective effects following traumatic brain injury (TBI). The TBI mouse model was induced using a controlled cortical impact method. Body weight, brain damage, motor function, and cognitive function were evaluated. Synaptogenesis markers were analyzed to investigate potential mechanisms of action. The animals were divided into six groups: sham, control, minocycline-treated group, and icariin-treated (3, 10, and 30 mg/kg, p. o.) groups. The icariin 30 mg/kg-treated group regained body weight at 7 and 8 d post TBI. Icariin 30 mg/kg- and 10 mg/kg-treated groups showed enhanced sensory-motor function at 8 d post TBI in rotarod and balance beam tests. Icariin-treated groups showed increased recognition index in the novel object recognition test at all doses and increased spontaneous alternation in the Y-maze test at 30 mg/kg. Icariin upregulated brain-derived neurotrophic factor, synaptophysin and postsynaptic density protein 95 expressions. However, no protective effects against brain damage or neuronal death were observed. The current results provide a basis for using icariin following TBI and suggest that it could be a candidate for the development of therapeutic agents for functional recovery after TBI.

Epimedii Herba: A Promising Herbal Medicine for Neuroplasticity.

Epimedii Herba (EH) is an herbal medicine originating from several plants of the genus Epimedium. It is a major therapeutic option for kidney yang deficiency syndrome, which is closely related to androgen hormones and also has been used to treat hemiplegia following a stroke in traditional medicine of Korea and PR China. To date, many clinical and basic researches of EH have shown the activities on functional recovery from brain diseases. Recently, neuroplasticity, which is the spontaneous reaction of the brain in response to diseases, has been shown to accelerate functional recovery. In addition, androgen hormones including testosterone are known to be the representative of neuroplasticity factors in the brain recovery processes. In this review, we described the neuro-pharmacological activities of EH, focusing on neuroplasticity. Thirty-three kinds of papers from MEDLINE/PubMed, EMBASE, and CNKI were identified and analyzed. We categorized the results into five types based on neuroplasticity mechanisms and presented the definition of each category and briefly described the results of these papers. Altogether, we can suggest that neuroplasticity is a novel viewpoint for guiding future brain research of EH and provide the evidence for the development of new clinical applications using EH in the treatment of brain diseases. Copyright © 2017 John Wiley & Sons, Ltd.

Protective Effects of Dihydrocaffeic Acid, a Coffee Component Metabolite, on a Focal Cerebral Ischemia Rat Model.

We recently reported the protective effects of chlorogenic acid (CGA) in a transient middle cerebral artery occlusion (tMCAo) rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA) was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion) were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP)-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p.) dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB) leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema.

Endothelium-Independent Vasorelaxant Effect of Ligusticum jeholense Root and Rhizoma on Rat Thoracic Aorta.

Ligusticum jeholense has been used as the traditional medicine 'Go-Bon' (Chinese name, Gao-ben) in China and Korea. Considering the increased use of medicinal herbs to treat hypertension, in this study, we aimed to investigate the mechanisms of the vasorelaxation effect caused by L. jeholense. We tested the methanol (MeOH) extract of L. jeholense root and rhizoma for vasorelaxant effects; while using an isolated organ-chamber technique, L. jeholense extract (LJE) induced relaxation in the rat aortic rings by stimulating vascular endothelial and smooth muscle cells. LJE showed concentration-dependent relaxant effects on endothelium-intact and endothelium-denuded aortic rings pre-contracted with both phenylephrine (PE) and potassium chloride (KCl) in Krebs-Henseleit (KH) buffer. The vasorelaxant effect of LJE was partly attenuated by pre-treatment with glibenclamide or 4-aminopyridine (4-AP) as K+ channel blockers. Moreover, LJE showed concentration-dependent inhibition of vasoconstriction by Ca2+ supplementation in the aortic rings that were pre-contracted with PE or KCl in Ca2+-free KH buffer. In addition, a combination of LJE and nifedipine, pre-incubated further, decreased PE-induced contractions. The results suggested that LJE-induced vasorelaxation were related to blocking K+ channels and inhibiting entry of extracellular Ca2+ via receptor-operative Ca2+ channels (ROCCs) or voltage-dependent Ca2+ channels (VDCCs).

Protective effect of Laminaria japonica with probiotics on murine colitis.

Inflammatory bowel disease (IBD) is a chronically relapsing inflammatory disorder of the gastrointestinal tract. Most IBD treatments are unsatisfactory; therefore, various dietary supplements have emerged as promising interventions. Laminaria japonica (LJ) is an edible seaweed used to regulate digestive symptoms. Probiotics have been reported to improve digestive problems and their simultaneous administration with seaweeds has been shown to produce synergistic therapeutic effects. Here, we investigated the effect of LJ combination with probiotics on dextran sodium sulfate-induced colitis model in mice. Aqueous LJ extracts (LJE) at doses from 100 to 300 mg/kg and probiotics at a dose of 300 mg/kg were orally administered for 7 days. Body weight, colon length, histological score, macroscopic damage, and the levels of cytokines IFN- γ , IL-1 ß , IL-6, IL-10, IL-12 (P40), IL-12 (P70), IL-17, and TNF- α were assessed. LJE alone caused a significant improvement of colitis signs such as colon length, histological score, and IL-1 ß and IL-6 production. LJE and probiotics demonstrated a synergistic effect by the histological score and levels of IL-1 ß , IL-6, and IL-12 (P40) but not IFN- γ , IL-10, and IL-12 (P70). In conclusion, LJE was effective in inducing protection against colitis in mice and acted synergistically with probiotics.

Sakuranetin as a Potential Regulator of Blood Pressure in Spontaneously Hypertensive Rats by Promoting Vasorelaxation through Calcium Channel Blockade.

Natural compounds, known for diverse pharmacological properties, have attracted attention as potential sources for hypertension treatment. Previous studies have revealed the hypotensive effect and vascular relaxation of prunetin, a natural compound derived from Prunus yedoensis. However, the potential blood pressure-lowering and vasorelaxant effects of sakuranetin, another representative compound found in plants belonging to the genus Prunus, have remained unexplored. We aimed to fill this gap by investigating the hypotensive and vasorelaxant effects of sakuranetin in rats. Results indicated that sakuranetin, particularly in the sakuranetin 20 mg/kg group, led to significant reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by -14.53 ± 5.64% and -19.83 ± 6.56% at 4 h after administration. In the sakuranetin 50 mg/kg group, the SBP and DBP decreased by -13.27 ± 6.86% and -16.62 ± 10.01% at 2 h and by -21.61 ± 4.49% and -30.45 ± 5.21% at 4 h after administration. In addition, we identified the vasorelaxant effects of sakuranetin, attributing its mechanisms to the inhibition of calcium influx and the modulation of angiotensin II. Considering its hypotensive and vasorelaxant effects, sakuranetin could potentially serve as an antihypertensive agent. However, further research is required to evaluate the safety and long-term efficacy.

Blood-Pressure-Lowering and Endothelium-Dependent Vasorelaxant Effects of Nutgall Tree in Rats.

Hypertension is the crucial modifiable risk factor for cardiovascular diseases, and efforts to identify functional foods that are effective for hypertension control are increasing. The nutgall tree (NT, Rhus chinensis Mill.) is used in traditional medicine and food because of its medicinal value. However, the role of NT in hypertension has not been investigated. Therefore, the hypotensive effect of NT leaf ethanol extract (NTE) was investigated in spontaneously hypertensive rats (SHRs). SHRs were allocated to three groups (control, 300, or 1000 mg/kg NTE), and blood pressure was measured before and after oral administration. Systolic and diastolic blood pressure significantly decreased in the NTE 1000 mg/kg group and was the lowest at 2 h after administration (-26.4 ± 10.3, -33.5 ± 9.8%, respectively). Daily NTE administration for five days also resulted in a similar effect. Further, the vasorelaxant effects and related mechanisms were investigated in the aortas of Sprague Dawley rats. NTE showed the dose-dependent blood-vessel-relaxing effect, and its mechanism involves the NO-sGC-cGMP pathway, activation of K+ channels, and reduction in the vasoconstrictive action of angiotensin II. Therefore, our study provides basic data indicating the potential use of NTE as a functional food for high blood pressure.

Influence of Feeding Time on a Non-steroidal Anti-inflammatory Drug-induced Small Intestinal Injury Mouse Model.

BACKGROUND/AIM: Non-steroidal anti-inflammatory drugs (NSAIDs), the most widely used pharmaceuticals, induce various adverse effects, including gastrointestinal injuries, such as ulcers and bleeding. Animal models of NSAID-induced small intestinal injury (NSI) have been extensively employed for the development of preventive and therapeutic agents. However, some experimental variations related to feeding times have been observed following NSI induction. This study aimed to investigate the impact of feeding time on an NSI mouse model. MATERIALS AND METHODS: The mice were divided into eight groups: normal, sham, and model groups (with feeding times of 2 h, 6 h, 10 h, 14 h, 18 h, and 22 h; n=10 in each group). The mice were fasted for 18 h before the injection of indomethacin (15 mg/kg, subcutaneously), except for the normal group. Food supply was halted at specific time points (2 h, 6 h, 10 h, 14 h, 18 h, and 22 h); however, the normal and sham groups were continuously fed throughout the experiment. The length of the small intestine was measured, and histological analysis was performed 24 h after induction. RESULTS: Up to 14 h after induction, NSI, indicated by small intestine shortening, remained consistent, with a reduction in length of approximately 10-20%. However, feeding for more than 14 h significantly exacerbated NSI, both anatomically and histologically. CONCLUSION: The ulcerative changes observed in the small intestine 14 h after indomethacin injection may be closely associated with the influence of food on NSI.

Prophylactic effects of Lonicera japonica extract on dextran sulphate sodium-induced colitis in a mouse model by the inhibition of the Th1/Th17 response.

Inflammatory bowel diseases (IBD) are chronically relapsing inflammatory disorders of the intestine. Although some therapeutic agents, including steroids, are available for the treatment of IBD, these agents have limited use. Therefore, dietary supplements have emerged as possible interventions for IBD. Japanese honeysuckle flower, the flower of Lonicera japonica, is a well-known dietary supplement and has been used to prevent or treat various inflammatory diseases. In the present study, we investigated the effects of L. japonica on experimental murine colitis. Colitis was induced by 5 % dextran sulphate sodium (DSS) in Balb/c mice. The water extract of L. japonica (LJE) at doses of 20, 100 or 500 mg/kg was orally administered to mice twice per day for 7 d. Body weight, colon length and a histological damage score were assessed to determine the effects on colitis. Cytokine profiles were assessed to examine the effects on helper T (Th) cell-related immunological responses. In addition, CD4⁺CD25⁺Foxp3⁺T cells were analysed in vivo and in vitro for investigating the effects on regulatory T (Treg) cells. LJE showed dose-dependent inhibitory effects against colon shortening, weight loss and histological damage. LJE down-regulated IL-1ß, TNF-α, interferon-γ, IL-6, IL-12 and IL-17. However, LJE did not show any significant effects on IL-10, IL-23, transforming growth factor-ß1 and Treg cell populations. In conclusion, LJE showed protective effects against DSS-induced colitis via the Th1/Th17 pathway and not via Treg cell-related mechanisms.

Vasorelaxant effect of Prunus yedoensis bark.

BACKGROUND: Prunus yedoensis Matsum. is used as traditional medicine-'Yaeng-Pi' or 'Hua-Pi'-in Japan and Korea. However, no studies have examined the pharmacological activities of the P. yedoensis bark. Only the antioxidant and antiviral activities of P. yedoensis fruit and the anti-hyperglycaemic effect of P. yedoensis leaf have been investigated. While studying the antihypertensive effects of several medicinal plants, we found that a methanol extract of P. yedoensis bark (MEPY) had distinct vasorelaxant effects on rat aortic rings. METHODS: The aortic rings were removed from Sprague-Dawley rats and suspended in organ chambers containing 10 ml Krebs-Henseleit solution. The aortic rings were placed between 2 tungsten stirrups and connected to an isometric force transducer. Changes in tension were recorded via isometric transducers connected to a data acquisition system. RESULTS: MEPY relaxed the contraction induced by phenylephrine (PE) both in endothelium-intact and endothelium-denuded aortic rings concentration dependently. However, the vasorelaxant effects of MEPY on endothelium-denuded aortic rings were lower than endothelium-intact aortic rings. The vasorelaxant effects of MEPY on endothelium-intact aortic rings were reduced by pre-treatment with L-NAME, methylene blue, or ODQ. However, pre-treatment with indomethacin, atropine, glibenclamide, tetraethylammonium, or 4-aminopyridine had no affection. In addition, MEPY inhibited the contraction induced by extracellular Ca(2+) in endothelium-denuded rat thoracic aorta rings pre-contracted by PE (1 µM) or KCl (60 mM) in Ca(2+)-free solution. CONCLUSIONS: Our results suggest that MEPY exerts its vasorelaxant effects via the activation of NO formation by means of L-Arg and NO-cGMP pathways and via the blockage of extracellular Ca(2+) channels.

Endothelium-independent vasorelaxation effects of Sigesbeckia glabrescens (Makino) Makino on isolated rat thoracic aorta.

The present study aimed to investigate the vasorelaxant effect of the methanol extract of Sigesbeckia glabrescens (Makino) Makino (MESG) on rat aortic rings and mechanism of action. MESG inhibited both noradrenaline bitartrate (NA)- and potassium chloride (KCl)-induced contraction of endothelium-intact aortic rings in a concentration-dependent manner. Removal of the endothelium did not influence the effect of MESG on NA-precontracted aortic rings. Pretreatment with MESG (250 µg/mL) inhibited calcium chloride-induced vasocontraction of NA- or KCl-precontracted endothelium-denuded aortic rings. It also relaxed phorbol-12-myristate-13-acetate-induced contraction of aortic rings in a concentration-dependent manner. In addition, Bay K8644 (an L-type calcium channel opener) vasocontracted in MESG pretreated aortic rings. On the other hand, the inositol 1,4,5-triphosphate receptor, the ryanodine receptor, the Rho-kinase inhibitor (Y-27632), a soluble guanylyl cyclase blocker (1-H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one), and K⁺ channel blockers (glybenclamide, tetraethylammonium, and 4-aminopyridine) did not affect the effect of MESG. These results suggested that the mechanism underlying the vasorelaxant effect of MESG is mediated by endothelium-independent pathways. This specifically refers to blockade of the influx of extracellular Ca²âº via receptor-operative Ca²âº channels and voltage-dependent Ca²âº channels and inhibition of a protein kinase C-mediated cellular pathway.

Lipocalin-2 Is a Key Regulator of Neuroinflammation in Secondary Traumatic and Ischemic Brain Injury.

Reactive glial cells are hallmarks of brain injury. However, whether these cells contribute to secondary inflammatory pathology and neurological deficits remains poorly understood. Lipocalin-2 (LCN2) has inflammatory and neurotoxic effects in various disease models; however, its pathogenic role in traumatic brain injury remains unknown. The aim of the present study was to investigate the expression of LCN2 and its role in neuroinflammation following brain injury. LCN2 expression was high in the mouse brain after controlled cortical impact (CCI) and photothrombotic stroke (PTS) injury. Brain levels of LCN2 mRNA and protein were also significantly higher in patients with chronic traumatic encephalopathy (CTE) than in normal subjects. RT-PCR and immunofluorescence analyses revealed that astrocytes were the major cellular source of LCN2 in the injured brain. Lcn2 deficiency or intracisternal injection of an LCN2 neutralizing antibody reduced CCI- and PTS-induced brain lesions, behavioral deficits, and neuroinflammation. Mechanistically, in cultured glial cells, recombinant LCN2 protein enhanced scratch injury-induced proinflammatory cytokine gene expression and inhibited Gdnf gene expression, whereas Lcn2 deficiency exerted opposite effects. Together, our results from CTE patients, rodent brain injury models, and cultured glial cells suggest that LCN2 mediates secondary damage response to traumatic and ischemic brain injury by promoting neuroinflammation and suppressing the expression of neurotropic factors.

Defatted sesame seed extract reduces brain oedema by regulating aquaporin 4 expression in acute phase of transient focal cerebral ischaemia in rat.

Brain oedema is the volumetric increase of brain tissue and is known to be linked to vascular factors, including the blood-brain barrier (BBB) and vascular permeability. Besides neuroprotection, inhibition of brain oedema also can be a method to protect the brain against ischaemic insult. Sesame is reported to have various beneficial effects on the cardiovascular and cerebrovascular systems. The neuroprotective effects of defatted sesame seed extract (DSE) in a transient middle cerebral artery occlusion (tMCAo) rat model were reported previously. The current study was planned to investigate whether the neuroprotective effects of DSE is related to brain oedema. The tMCAo rat model was used to investigate the brain water content (BWC) and Evans blue (EB) leakage. Aquaporin 4 (AQP4), matrix metalloproteinase (MMP)-2 and MMP-9 expressions at 4 and 24 h after ischaemia were analysed. In vitro zymography was performed to investigate the effects on MMPs activities. DSE (30, 100, and 300 mg/kg, p.o.) reduced BWC but not EB leakage. DSE inhibited AQP4 expression at 4 h but not at 24 h after ischaemia. It did not show any effects on MMPs expressions and activities. Therefore, DSE might be effective on brain oedema by AQP4 regulation during the acute phase of ischaemia.

Effects of Angelica acutiloba on mast cell-mediated allergic reactions in vitro and in vivo.

The root of Angelica acutiloba is a widely used herbal medicine which has been used as a typical therapeutic for allergic diseases in traditional medicine. This study was aimed to investigate the effects of A. acutiloba on allergic reactions in in vitro and in vivo models and its mechanism of action. A. acutiloba was extracted by maceration with 80% ethanol (AAE) and standardized by high-performance liquid chromatography. We investigated the effect of AAE on phorbol-12-myristate-13-acetate plus calcium ionophore A23187 (PMACI)-induced cytokine release; phosphorylation of JNK, ERK, and p38 in human mast cell-1 (HMC-1); and compound 48/80-induced release of histamine in rat peritoneal mast cells (RPMCs). We also investigated the effects on Evans blue (EB) extravasation induced by anti-DNP IgE in rats. Treatment with 1, 10 and 100 µg/ml AAE concentration-dependently inhibited the release of cytokines (tumor necrosis factor-α, interleukin (IL) -6, and IL-8) and phosphorylation of ERK and JNK induced by PMACI in HMC-1 cells, but it did not inhibit the phosphorylation of p38. It also inhibited compound 48/80-induced histamine release in RPMCs. Oral administration of 271 mg/kg AAE inhibited EB extravasation in a passive cutaneous anaphylaxis rat model. In conclusion, AAE inhibited mast cell-derived allergic reactions by inhibiting the release of histamine, the production of pro-inflammatory cytokines, and the phosphorylation of ERK and JNK.

Protective effects of Galla Rhois, the excrescence produced by the sumac aphid, Schlechtendalia chinensis, on transient focal cerebral ischemia in the rat.

Galla Rhois is formed by aphids, primarily Schlechtendalia chinensis Bell (Homoptera: Pemphigidae), on the leaf of sumac, Rhus javanica L. (Sapindales: Anacardiaceae). It is a tannin-rich herb that is widely used in traditional Korean medicine. Its various pharmacological effects, including its radical-scavenging effects, have been reported. The purpose of the current study was to determine if these radical-scavenging effects can be confirmed using in vitro assays and to investigate its neuroprotective effects, optimal dosage, mechanisms, and therapeutic time window in an animal model of stroke. Galla Rhois 85% methanol extract (GRE) exhibited potent and dose-dependent radical-scavenging effects on various radicals. Oral administration of GRE (300 mg/kg) in a transient focal cerebral ischemia rat model (two hours of occlusion followed by 22 hours of reperfusion) reduced the brain infarct volume by 37.5%. It also improved sensory motor function and reduced lipid-peroxidation in middle cerebral artery occlusion. However, it did not have any inhibitory effects on brain edema. The time window study revealed that pre- and co-treatment with GRE had protective effects, but post-treatment with GRE (three or six hours after ischemia) did not have protective effects. In conclusion, GRE had potent radical-scavenging activities and neuroprotective effects in a rat model of stroke when it was pre- and co-administered. The optimal dosage may be around 300 mg/kg for oral administration.

Therapeutic Potential of Chungsangboha-tang for the Treatment of Asthma: A Review of Preclinical and Clinical Studies.

In traditional Korean medicine, Chungsangboha-tang (CSBHT) and its modified forms are used to treat various respiratory disorders, including asthma. This study aimed to identify research trends, clarify the effectiveness of CSBHT and related prescriptions, and lay a foundation for future research. We conducted a literature review using PubMed, Embase, Google Scholar, Oriental Medicine Advanced Searching Integrated System, National Digital Science Links, Korean Medical Database, Wanfang Data, and Chinese National Knowledge Infrastructure databases. We analyzed 25 studies, including 5 in vitro studies, 6 animal studies, and 14 human studies. Many studies evaluated the efficacy of CSBHT and its related prescriptions, including experimental studies on its effectiveness in asthma. The main mechanism of action involves the anti-inflammatory effect caused by the regulation of various immune cells, cytokines, and chemokines. In addition, clinical trials on asthma reported the benefits of CSBHT and its related prescriptions. However, there has been no randomized controlled study of clinical trials on the clinical effectiveness of CSBHT in asthma. Therefore, large-scale randomized controlled studies should be conducted in the future.

Modified Protocol to Enable the Study of Hemorrhage and Hematoma in a Traumatic Brain Injury Mouse Model.

To date, many studies using the controlled cortical impact (CCI) mouse model of traumatic brain injury (TBI) have presented results without presenting the pathophysiology of the injury-core itself or the temporal features of hemorrhage (Hrr). This might be owing to the removal of the injury-core during the histological procedure. We therefore developed a modified protocol to preserve the injury-core. The heads of mice were obtained after perfusion and were post-fixed. The brains were then harvested, retaining the ipsilateral skull bone; these were post-fixed again and sliced using a cryocut. To validate the utility of the procedure, the temporal pattern of Hrr depending on the impacting depth was analyzed. CCI-TBI was induced at the following depths: 1.5 mm (mild Hrr), 2.5 mm (moderate Hrr), and 3.5 mm (severe Hrr). A pharmacological study was also conducted using hemodynamic agents such as warfarin (2 mg/kg) and coagulation factor VIIa (Coa-VIIa, 1 mg/kg). The current protocol enabled the visual observation of the Hrr until 7 days. Hrr peaked at 1-3 days and then decreased to the normal range on the seventh day. It expanded from the affected cortex (mild) to the periphery of the hippocampus (moderate) and the brain ventricle (severe). Pharmacological studies showed that warfarin pre-treatment produced a massively increased Hrr, concurrent with the highest mortality rate and brain injury. Coa-VIIa reduced the side effects of warfarin. Therefore, these results suggest that the current method might be suitable to conduct studies on hemorrhage, hematoma, and the injury-core in experiments using the CCI-TBI mouse model.

Efficacy of complementary medicine for nonsteroidal anti-inflammatory drug-induced small intestinal injuries: A narrative review.

ABSTRACT: Nonsteroidal anti-inflammatory drug-induced small bowel injuries (NSIs) have been largely ignored for decades due to the focus on nonsteroidal anti-inflammatory drug gastropathy. With the visualization of the small intestines enabled by video capsule endoscopy, the frequency and severity of NSIs have become more evident. NSIs have a complex pathophysiology, and no effective preventive or treatment options have been proven. Complementary and alternative medicine (CAM) has been used to treat disorders of the small intestine, and more research on its effectiveness for NSIs has been conducted.We reviewed the current evidence and mechanisms of action of CAMs on NSI. Clinical and experimental studies on the effect of CAMs on NSIs were performed using 10 databases.Twenty-two studies (3 clinical and 19 in vivo experimental studies) were included in the final analysis involving 10 kinds of CAMs: bovine colostrum, Orengedokuto (coptis), muscovite, licorice, grape seed, wheat, brown seaweed, Ganoderma lucidum fungus mycelia, Chaenomeles speciosa (sweet) Nakai (muguasantie), and Jinghua Weikang capsule. The mechanisms of CAM include an increase in prostaglandin E2, reparation of the enteric nervous system, inhibition of pro-inflammatory cytokines, reduction of intestinal permeability and enteric bacterial numbers, decrease in oxidative stress, and modulation of small intestinal motility.CAM may be a novel alternative option for treating and preventing NSI, and further studies on human and animal models with relevant comorbidities are warranted.