Antidepressant-like Effects of Chinese Quince (Chaenomeles sinensis) Fruit Based on In Vivo and Molecular Docking Studies.

In this study, we examined the potential antidepressant-like effects of Chinese quince fruit extract (Chaenomeles sinensis fruit extract, CSFE) in an in vivo model induced by repeated injection of corticosterone (CORT)-induced depression. HPLC analysis determined that chlorogenic acid (CGA), neo-chlorogenic acid (neo-CGA), and rutin (RT) compounds were major constituents in CSFE. Male ICR mice (5 weeks old) were orally administered various doses (30, 100, and 300 mg/kg) of CSFE and selegiline (10 mg/kg), a monoamine oxidase B (MAO-B) inhibitor, as a positive control following daily intraperitoneal injections of CORT (40 mg/kg) for 21 days. In our results, mice treated with CSFE exhibited significant improvements in depressive-like behaviors induced by CORT. This was evidenced by reduced immobility times in the tail suspension test and forced swim test, as well as increased step-through latency times in the passive avoidance test. Indeed, mice treated with CSFE also exhibited a significant decrease in anxiety-like behaviors as measured by the elevated plus maze test. Moreover, molecular docking analysis indicated that CGA and neo-CGA from CSFE had stronger binding to the active site of MAO-B. Our results indicate that CSFE has potential antidepressant effects in a mouse model of repeated injections of CORT-induced depression.

Atractylodes macrocephala Koidz Alleviates Symptoms in Zymosan-Induced Irritable Bowel Syndrome Mouse Model through TRPV1, NaV1.5, and NaV1.7 Channel Modulation.

(1) Background: Irritable bowel syndrome (IBS) is a common disease in the gastrointestinal (GI) tract. Atractylodes macrocephala Koidz (AMK) is known as one of the traditional medicines that shows a good efficacy in the GI tract. (2) Methods: We investigated the effect of AMK in a network pharmacology and zymosan-induced IBS animal model. In addition, we performed electrophysiological experiments to confirm the regulatory mechanisms related to IBS. (3) Results: Various characteristics of AMK were investigated using TCMSP data and various analysis systems. AMK restored the macroscopic changes and weight to normal. Colonic mucosa and inflammatory factors were reduced. These effects were similar to those of amitriptyline and sulfasalazine. In addition, transient receptor potential (TRP) V1, voltage-gated Na+ (NaV) 1.5, and NaV1.7 channels were inhibited. (4) Conclusion: These results suggest that AMK may be a promising therapeutic candidate for IBS management through the regulation of ion channels.

Exploring the Therapeutic Effects of Atractylodes macrocephala Koidz against Human Gastric Cancer.

Atractylodes macrocephala Koidz (AMK) is a traditional herbal medicine used for thousands of years in East Asia to improve a variety of illnesses and conditions, including cancers. This study explored the effect of AMK extract on apoptosis and tumor-grafted mice using AGS human gastric adenocarcinoma cells. We investigated the compounds, target genes, and associated diseases of AMK using the Traditional Chinese Medical Systems Pharmacy (TCMSP) database platform. Cell viability assay, cell cycle and mitochondrial depolarization analysis, caspase activity assay, reactive oxygen species (ROS) assay, and wound healing and spheroid formation assay were used to investigate the anti-cancer effects of AMK extract on AGS cells. Also, in vivo studies were conducted using subcutaneous xenografts. AMK extract reduced the viability of AGS cells and increased the sub-G1 cell fraction and the mitochondrial membrane potential. Also, AMK extract increased the production of ROS. AMK extract induced the increased caspase activities and modulated the mitogen-activated protein kinases (MAPK). In addition, AMK extract effectively inhibited AGS cell migration and led to a notable reduction in the growth of AGS spheroids. Moreover, AMK extract hindered the growth of AGS xenograft tumors in NSG mice. Our results suggest that AMK has anti-cancer effects by promoting cell cycle arrest and inhibiting the proliferation of AGS cancer cells and a xenograft model through apoptosis. This study could provide a novel approach to treat gastric cancer.

Environmental Enrichment for Stroke and Traumatic Brain Injury: Mechanisms and Translational Implications.

Acquired brain injuries, such as ischemic stroke, intracerebral hemorrhage (ICH), and traumatic brain injury (TBI), can cause severe neurologic damage and even death. Unfortunately, currently, there are no effective and safe treatments to reduce the high disability and mortality rates associated with these brain injuries. However, environmental enrichment (EE) is an emerging approach to treating and rehabilitating acquired brain injuries by promoting motor, sensory, and social stimulation. Multiple preclinical studies have shown that EE benefits functional recovery, including improved motor and cognitive function and psychological benefits mediated by complex protective signaling pathways. This article provides an overview of the enriched environment protocols used in animal models of ischemic stroke, ICH, and TBI, as well as relevant clinical studies, with a particular focus on ischemic stroke. Additionally, we explored studies of animals with stroke and TBI exposed to EE alone or in combination with multiple drugs and other rehabilitation modalities. Finally, we discuss the potential clinical applications of EE in future brain rehabilitation therapy and the molecular and cellular changes caused by EE in rodents with stroke or TBI. This article aims to advance preclinical and clinical research on EE rehabilitation therapy for acquired brain injury. © 2024 American Physiological Society. Compr Physiol 14:5291-5323, 2024.

Effects of Natural Product-Derived Compounds on Inflammatory Pain via Regulation of Microglial Activation.

Inflammatory pain is a type of pain caused by tissue damage associated with inflammation and is characterized by hypersensitivity to pain and neuroinflammation in the spinal cord. Neuroinflammation is significantly increased by various neurotransmitters and cytokines that are expressed in activated primary afferent neurons, and it plays a pivotal role in the development of inflammatory pain. The activation of microglia and elevated levels of pro-inflammatory cytokines are the hallmark features of neuroinflammation. During the development of neuroinflammation, various intracellular signaling pathways are activated or inhibited in microglia, leading to the regulation of inflammatory proteins and cytokines. Numerous attempts have been conducted to alleviate inflammatory pain by inhibiting microglial activation. Natural products and their compounds have gained attention as potential candidates for suppressing inflammatory pain due to verified safety through centuries of use. Many studies have also shown that natural product-derived compounds have the potential to suppress microglial activation and alleviate inflammatory pain. Herein, we review the literature on inflammatory mediators and intracellular signaling involved in microglial activation in inflammatory pain, as well as natural product-derived compounds that have been found to suppress microglial activation. This review suggests that natural product-derived compounds have the potential to alleviate inflammatory pain through the suppression of microglial activation.

3,5-Dicaffeoylquinic acid attenuates microglial activation-mediated inflammatory pain by enhancing autophagy through the suppression of MCP3/JAK2/STAT3 signaling.

Microglial activation in the spinal cord contributes to the development of inflammatory pain. Monocyte chemotactic protein 3 (MCP3) can induce microglial activation, resulting in increased pain sensitivity; however, the underlying mechanism remains poorly understood. 3,5-dicaffeoylquinic acid (3,5-DCQA) has shown protective effects against inflammation-related diseases, but the effect of 3,5-DCQA on microglial activation and inflammatory pain is not evaluated. This study aimed to investigate the effects of 3,5-DCQA on microglial activation-induced inflammatory pain. Furthermore, the underlying mechanism inhibited by 3,5-DCQA via MCP3 suppression was studied. To induce microglial activation, LPS was treated in BV2 microglial cells. The LPS-induced microglial activation and pro-inflammatory cytokines production were significantly reduced by 3,5-DCQA treatment in BV2 cells. Moreover, 3,5-DCQA suppressed LPS-induced MCP3 expression, resulting in reduced phosphorylation of JAK2/STAT3. Interestingly, the suppressed JAK2/STAT3 signaling enhanced autophagy induction in BV2 cells. The increased autophagy by 3,5-DCQA and knockout of MCP3 inhibited LPS-induced inflammatory response in BV2 cells. To establish the inflammatory pain, CFA was injected into the right paw of mice. The CFA-induced pain hypersensitivity and foot swelling were attenuated by the oral administration of 3,5-DCQA. Moreover, CFA-induced microglial activation was reduced and the autophagy markers were recovered in the spinal cord of 3,5-DCQA-administered mice. Similar results were observed in cultured primary microglia. Our findings indicate that 3,5-DCQA attenuates inflammation-mediated pain hypersensitivity by enhancing autophagy through inhibition of MCP3-induced JAK2/STAT3 signaling. Therefore, 3,5-DCQA could be a potential therapeutic agent for alleviating inflammatory pain.

Effects of black garlic on the pacemaker potentials of interstitial cells of Cajal in murine small intestine in vitro and on gastrointestinal motility in vivo.

Black garlic (BG) is a newly explored food stuff obtained via fermentation of raw, healthy garlic, especially in Asian countries. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal (GI) motility. The purpose of this study was to investigate the effects of BG extract on the pacemaker potentials of the ICC in the small intestines of mice and the possibility of controlling GI motility. The antioxidant activity of BG extract was also investigated. The whole-cell electrophysiological method was used to measure pacemaker potentials of the ICC in vitro, whereas GI motility was measured using the intestinal transit rate (ITR) in vivo. BG extract depolarized the pacemaker potentials of the ICC. Y25130 and RS39604 5-HT receptor antagonists could not inhibit the effect of BG extract on the pacemaker potentials of the ICC, whereas the 5-HT receptor antagonist SB269970 could. Pre-treatment with external Na+ (5 mM) or Ca2+-free solution inhibited the BG extract-induced depolarization of the ICC. With SB203580, PD98059, or c-jun NH2-terminal kinase II inhibitor pre-treatment, BG extract did not induce pacemaker potential depolarization. Moreover, the ITR values were increased by BG extract. Elevation of the ITR due to BG extract was related with increased protein expression of the 5-HT7 receptors. In addition, BG extract showed antioxidant activity. Collectively, these results highlight the ability of BG extract to regulate GI motility and the possibility of using it to develop GI motility modulators in the future. Moreover, BG showed immense potential as an antioxidant.

The Antinociceptive Potential of Camellia japonica Leaf Extract, (-)-Epicatechin, and Rutin against Chronic Constriction Injury-Induced Neuropathic Pain in Rats.

Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. Camellia japonica leaves are known to have antioxidant and anti-inflammatory properties.; however, their antinociceptive efficacy has not yet been explored. We examined the antinociceptive efficacy and underlying mechanism of C. japonica leaf extract (CJE) in chronic constriction injury (CCI)-induced neuropathic pain models. To test the antinociceptive activity of CJE, three types of allodynia were evaluated: punctate allodynia using von Frey filaments, dynamic allodynia using a paintbrush and cotton swab, and cold allodynia using a cold plate test. CCI rats developed neuropathic pain representing increases in the three types of allodynia and spontaneous pain. In addition, CCI rats showed high phosphorylation levels of mitogen-activated protein kinases (MAPKs), transcription factors, and nociceptive mediators in dorsal root ganglion (DRG). The ionized calcium-binding adapter molecule 1 levels and neuroinflammation also increased following CCI surgery in the spinal cord. CJE and its active components have potential antinociceptive effects against CCI-induced neuropathic pain that might be mediated by MAPK activation in the DRG and microglial activation in the spinal cord. These findings suggest that CJE, (-)-epicatechin, and rutin could be novel candidates for neuropathic pain management.

Alisma canaliculatum Extract Affects AGS Gastric Cancer Cells by Inducing Apoptosis.

The anti-cancer effects of Alisma canaliculatum extracts (ACE) were identified in AGS gastric cancer cells. Our results showed that ACE inhibited the growth of AGS cells, increased the proportion of sub-G1 phase cells, and depolarized the membrane potential of mitochondria. ACE-induced gastric cancer cell death was associated with Bcl-2, survivin and Bax level changes, and it activated caspase-3 and -9. In addition, it was involved in the activation of MAPKs and increased the reactive oxygen species (ROS). These results suggest that ACE induces apoptosis in AGS gastric cancer cells, and therefore, ACE may have the potential to treat gastric cancer.

Salvia miltiorrhiza induces depolarization of pacemaker potentials in murine small intestinal interstitial cells of Cajal via extracellular Ca2+ and Na+ influx.

Interstitial cells of Cajal (ICCs) are pacemaker cells that control smooth muscle contraction in the gastrointestinal (GI) tract. The present study investigated the effects of Salvia miltiorrhiza (SM) on the pacemaker potentials of ICCs from the mouse small intestine in vitro and on GI motility in vivo. The whole­cell patch­clamp configuration was used to record pacemaker potential in ICCs in vitro, and GI motility was investigated in vivo by recording intestinal transit rate (ITR). Using the whole­cell patch­clamp configuration, SM depolarized the pacemaker potentials of ICCs in a dose­dependent manner. Fulvestrant blocked SM­induced effects but 1,3­dihydro­3,3­bis(4­hydroxyphenyl)-7-methyl­2H­indol­2­one did not. Additionally, 4­[2­phenyl-5,7­bis(trifluoromethyl) pyrazolo[1,5­a]pyrimidin­3­yl] phenol blocked SM­induced effects. Intracellular guanosine 5'­O­(2­thiodiphosphate), and pretreatment with extracellular Ca2+­ and Na+­free solutions also blocked SM­induced effects. Furthermore, ITR values were increased by SM in vivo and SM elevated the levels of motilin (MTL). The SM­induced increase in ITR was associated with increased protein expression levels of c­kit and the transmembrane protein 16A (TMEM16A) channel. In addition, SM induced pacemaker potential depolarization through estrogen receptor ß in a G protein­dependent manner via extracellular Ca2+ and Na+ regulation in the murine small intestine in vitro. Moreover, SM increased the ITR in vivo through the MTL hormone via c­kit and TMEM16A­dependent pathways. Taken together, these results suggested that SM may have the ability to control GI motility and could be used as a GI motility regulator.

Anti-Inflammatory Effects of Asian Fawn Lily (Erythronium japonicum) Extract on Lipopolysaccharide-Induced Depressive-Like Behavior in Mice.

Neuroinflammation is associated with an increased risk of depression. Lipopolysaccharide (LPS) treatment is known to induce pro-inflammatory cytokine secretion and a depressive-like phenotype in mice. Although Erythronium japonicum exhibits various health benefits, the role of E. japonicum extract (EJE) in inflammation-associated depression is unknown. This study aimed to explore the anti-inflammatory effect of EJE on LPS-induced depressive symptoms in mice using the open field test (OFT), passive avoidance test (PAT), tail suspension test (TST), and forced swim test (FST). LPS-treated mice had significantly increased immobility time in the TST and FST, decreased step-through latency time in the PAT, and decreased locomotor activity in the OFT. However, administration of 100 and 300 mg/kg of EJE significantly improved these depressive-like behaviors. EJE also prevented the increase in mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and monocyte chemoattractant protein-1 (MCP-1), and the decrease in IL-10 levels by inhibiting nuclear factor-κB (NF-κB) subunit p65 phosphorylation. Additionally, LPS-treated mice showed markedly decreased brain-derived neurotrophic factor (BDNF) levels and phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt, while EJE treatment significantly increased these levels in the hippocampus. These results suggest that EJE ameliorated LPS-induced depressive-like behavior by reducing LPS-induced neuroinflammation and activating the BDNF-PI3K/Akt pathway.

Dicaffeoylquinic acids alleviate memory loss via reduction of oxidative stress in stress-hormone-induced depressive mice.

Chronic stress can lead to depression due to elevated levels of stress hormones such as glucocorticoid. This is accompanied by an increase in reactive oxygen species (ROS) levels in the brain, which can cause dendritic spine loss and atrophy in neurons, followed by memory loss. Dicaffeoylquinic acids (diCQAs) are naturally occurring polyphenolic antioxidant compounds in Arctium lappa extracts (AL). The effects of natural derivatives of cafferoylqunic acid on stress hormone-induced depressive behavior and their underlying mechanisms are uncertain. In the current study, we showed that diCQAs reduced depressive behaviors including memory loss in corticosterone (CORT) treated mice. The mechanism of anti-depressants of diCQAs is likely through reduction of ROS production by inhibiting the activity of monoamine oxidase (MAO) type A and B in neurons and astrocytes. Among diCQAs, 3,4- and 3,5-diCQA significantly inhibited the activity of MAO enzymes followed by the reduction of ROS in neurons and astrocytes and also protected neuronal atrophy and synaptic transmission against stress hormone. These results suggest that 3,4- and 3,5-diCQAs effectively reduced depressive symptoms and inhibited ROS production to alleviate memory loss in stress hormone-induced depressive mice and hence, which provide some potential natural antidepressants.

Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway.

Imipramine (IMI) is a tricyclic synthetic antidepressant that is used to treat chronic psychiatric disorders, including depression and neuropathic pain. IMI also has inhibitory effects against various cancer types, including prostate cancer; however, the mechanism of its anticancer activity is not well understood. In the present study, we investigated the antimetastatic and anti-invasive effects of IMI in metastatic castration-resistant prostate cancer PC-3 cells, with an emphasis on the serine/threonine protein kinase AKT-mediated nuclear factor kappa B (NF-κB) signaling pathway. While IMI did not induce cell death, it attenuated PC-3 cell proliferation. According to the wound healing assay and invasion assay, migration and invasion in PC-3 cells were significantly inhibited by IMI in a dose-dependent manner. IMI significantly downregulated p-AKT protein expression but upregulated phospho-extracellular signal-regulated kinase (ERK1)/2 protein expression levels. Furthermore, IMI treatment resulted in decreased AKT-mediated downstream signaling, including p-inhibitor of κB kinase (IKK)α/ß, p-inhibitor of κB (IκBα), and p-p65. Inhibited NF-κB signaling reduced the secretion of several proinflammatory cytokines and chemokine by PC-3 cells. Overall, our study explored the negative correlation between the use of antidepressants and prostate cancer progression, showing that IMI attenuated cell viability, migration, and invasion of PC-3 cells by suppressing the expression of AKT and NF-κB-related signaling proteins and secretion of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1).

The Effect of Lactobacillus acidophilus YT1 (MENOLACTO) on Improving Menopausal Symptoms: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

This study evaluated the efficacy of Lactobacillus acidophilus YT1 (MENOLACTO) for alleviating menopausal symptoms. This study was a multi-center, randomized, double-blinded, placebo-controlled clinical trial involving female subjects (ages: 40-60 years) with menopausal symptoms and a Kupperman index (KMI) score ≥ 20. Subjects were administered 1 × 108 CFU/day MENOLACTO or placebo, with the primary endpoint being total KMI score, and the effect of secondary endpoints on alleviating menopausal symptoms according to individual categories of the modified KMI, as well as a quality of life questionnaire (MENQOL questionnaire). After 12 weeks, total KMI scores decreased significantly, demonstrating improved menopausal symptoms relative to placebo along with improved modified KMI scores. Additionally, quality of life, according to the MENQOL questionnaire, significantly improved in all four symptoms-physical, psychosocial, vasomotor, and sexual symptoms. Moreover, we observed no significant difference between the two groups or significant changes in blood follicle-stimulating hormone and estradiol levels or endometrial thickness. These results demonstrated that MENOLACTO alleviated menopausal symptoms without notable side effects and improved quality of life, suggesting its efficacy as an alternative supplement to alleviate menopausal symptoms in women ineligible for hormonal therapy.

Erythronium japonicum Alleviates Inflammatory Pain by Inhibiting MAPK Activation and by Suppressing NF-κB Activation via ERK/Nrf2/HO-1 Signaling Pathway.

Microglial activation-mediated neuroinflammation influences the development of inflammatory pain. The aim of this study was to investigate the anti-inflammatory effects and mechanisms of aqueous Erythronium japonicum extract (EJE) in microglia activation-mediated inflammatory pain. EJE was found to suppress lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), ionized calcium-binding adapter molecule 1 (IBA-1), and pro-inflammatory cytokines in BV2 microglial cells. In addition, LPS-induced c-Jun NH2 terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation were inhibited by EJE. Intriguingly, EJE also inhibited p65 phosphorylation by activating extracellular signal-regulated kinase-1/2 (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Furthermore, the effects of EJE treatment, such as HO-1 induction and the reduction of NF-ĸB activation, were reversed by ERK1/2 inhibition. In an inflammatory pain mouse model, Complete Freund's Adjuvant (CFA)-induced mechanical allodynia and foot swelling were alleviated by the oral administration of EJE. Consistent with in vitro results, EJE increased HO-1, while decreasing CFA-induced COX-2, IBA-1, and pro-inflammatory cytokines in the spinal cord. Among the components of EJE, butanol most heavily suppressed LPS-induced microglial activation and increased HO-1 expression. These findings indicate that EJE can alleviate inflammatory pain by inhibiting p38 and JNK and by suppressing NF-ĸB via ERK/Nrf2/HO-1 signaling.

Suppressive Effect of Arctium Lappa L. Leaves on Retinal Damage Against A2E-Induced ARPE-19 Cells and Mice.

Age-related macular degeneration (AMD) is a major cause of irreversible loss of vision with 80-90% of patients demonstrating dry type AMD. Dry AMD could possibly be prevented by polyphenol-rich medicinal foods by the inhibition of N-retinylidene-N-retinylethanolamine (A2E)-induced oxidative stress and cell damage. Arctium lappa L. (AL) leaves are medicinal and have antioxidant activity. The purpose of this study was to elucidate the protective effects of the extract of AL leaves (ALE) on dry AMD models, including in vitro A2E-induced damage in ARPE-19 cells, a human retinal pigment epithelial cell line, and in vivo light-induced retinal damage in BALB/c mice. According to the total phenolic contents (TPCs), total flavonoid contents (TFCs) and antioxidant activities, ALE was rich in polyphenols and had antioxidant efficacies on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2',7'-dichlorofluorescin diacetate (DCFDA) assays. The effects of ALE on A2E accumulation and A2E-induced cell death were also monitored. Despite continued exposure to A2E (10 µM), ALE attenuated A2E accumulation in APRE-19 cells with levels similar to lutein. A2E-induced cell death at high concentration (25 µM) was also suppressed by ALE by inhibiting the apoptotic signaling pathway. Furthermore, ALE could protect the outer nuclear layer (ONL) in the retina from light-induced AMD in BALB/c mice. In conclusion, ALE could be considered a potentially valuable medicinal food for dry AMD.

Memory-enhancing effects of Ishige foliacea extract: In vitro and in vivo study.

Ishige foliacea is used as a functional food in East-Asian countries. We evaluated the memory-enhancing effect of an ethanol extract of I. foliacea (EEI) using in vitro and in vivo models. In vitro acetylcholinesterase and ß-secretase inhibitory activities, antioxidant properties, and neuroprotective effects against human neuronal cell death by H2 O2 and ß-amyloid (Aß) were investigated. We explored the memory-enhancing effect and its underlying mechanism in a mouse model of scopolamine (SCO)-induced memory deficits. EEI showed free radical scavenging and acetylcholinesterase and ß-secretase inhibition activities. Additionally, EEI significantly decreased neuronal cell death induced by H2 O2 or Aß in human neuroblastoma SH-SY5Y cells. In behavior tests, SCO-induced memory deficits was improved by EEI administration. EEI increased the protein expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) and phosphorylated extracellular signal-regulated kinase, which are related to synaptic plasticity in the hippocampus. EEI may ameliorate memory deficits and prevent neurodegenerative disorders. PRACTICAL APPLICATIONS: As the population ages, dementia, a neurodegenerative disease, is becoming an important problem. Various Alzheimer's drugs have been developed based on the disease mechanism, but alternative treatments are required because of the low bioavailability and hepatotoxicity of current medications. Ishige foliacea is a type of brown algae containing various bioactive substances. Phlorotannins, known as brown algae polyphenols, have been studied for their various functionalities such as, anticancer, anti-obesity, antioxidant, and sleep improvement effects, and have attracted attention as raw materials for developing new natural products. We found that the EEI mitigates SCO-induced damage by protecting neurons from oxidative stress-induced cell damage, controlling synthesis mechanisms of the causative agents of AD, and activating BDNF-TrkB-ERK signaling to promote memory function in the hippocampus. The results of this study can serve as a foundation for further research. Additionally, I. foliacea may be useful for treating and improving AD.

Administration of Asian Herb Bennet (Geum japonicum) Extract Reverses Depressive-Like Behaviors in Mouse Model of Depression Induced by Corticosterone.

Geum japonicum, commonly known as Asian herb bennet, has been used as a diuretic, astringent, anti-dizziness, and anti-headache agent in traditional medicine. Since the antidepressant-like effects of G. japonicum extract have not been well studied, we examined the antidepressant-like effects of G. japonicum extract using depressive-like behavior induced in mice through daily injection of corticosterone (CORT). ICR mice (male, 8 weeks old) were treated with CORT (40 mg/kg, i.p.) and orally administered using oral gavage needles with G. japonicum extract (30, 100, and 300 mg/kg) for 4 weeks. Behavioral experiments were performed 1 h after administration. The control mice exhibited a significant increase in the immobility times in the tail suspension and forced swim tests as well as the step-through latency time in the passive avoidance test. Further, the control group showed a significant decrease in their sucrose consumption. However, treatment with G. japonicum extract at doses of 100 and 300 mg/kg significantly improved these depression-like behaviors without altering the locomotor activity. Moreover, treatment with G. japonicum extract significantly prevented the decrease in the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In addition, G. japonicum extract had neuroprotective effects against CORT-induced neurotoxicity in SH-SY5Y cells. Our study indicates that G. japonicum extract exhibits antidepressant-like activity in CORT-induced depressive mice, which might be as a result of increased BDNF expression.

Poria cocus Wolf Extract Ameliorates Hepatic Steatosis through Regulation of Lipid Metabolism, Inhibition of ER Stress, and Activation of Autophagy via AMPK Activation.

Poria cocos Wolf (PCW) is an edible, pharmaceutical mushroom with remarkable biological properties including anti-tumor, anti-inflammation, anti-oxidation, anti-ageing, and anti-diabetic effects. In the current study, we investigated the effects of PCW extract on hepatic steatosis under in vitro and in vivo conditions, and elucidated the underlying mechanisms. In this study, a mixture of HepG2 cells treated with free fatty acid (FFA)-palmitic and oleic acid-and high-fat diet (HFD)-fed obese mice were used; in this background, the triglyceride (TG) levels in HepG2 cells and mice liver were measured, and the expression levels of genes associated with lipogenesis, fatty acid oxidation, endoplasmic reticulum (ER) stress, and autophagy were determined. Treatment of HepG2 cells with FFA enhanced intracellular TG levels in HepG2 cells, but co-treatment with PCW significantly attenuated the TG levels. Notably, PCW significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein-1c (SREBP-1c) in FFA-treated HepG2 cells. PCW downregulated the expression of lipogenesis-related genes, but upregulated the expression of genes associated with fatty acid oxidation. Further, PCW inhibited FFA-induced expression of ER stress markers and induced autophagy proteins. However, inhibition of AMPK significantly attenuated the beneficial effects of PCW in HepG2 cells. Moreover, PCW efficiently decreased HFD-induced hepatic TG accumulation in vivo and increased the phosphorylation of hepatic AMPK. Three compounds present in PCW including poricoic acid, pachymic acid, and ergosterol, significantly decreased FFA-induced increase in intracellular TG levels, consistent with increased AMPK phosphorylation, suggesting that poricoic acid, pachymic acid, and ergosterol are responsible for PCW-mediated amelioration of hepatic steatosis. Taken together, these results demonstrated that PCW ameliorates hepatic steatosis through the regulation of lipid metabolism, inhibition of ER stress, and activation of autophagy in an AMPK-dependent manner. This suggested that PCW can be potentially used for the treatment of hepatic steatosis.

Analgesic Effects of Cnidium officinale Extracts on Postoperative, Neuropathic, and Menopausal Pain in Rat Models.

Cnidium officinale, widely cultivated in East Asia, has been reported to exhibit pharmacological efficacy in various disorders. However, little has been reported on its role as a pain killer. In this study, we reveal that the C. officinale extract (COE) has great efficacy as a novel analgesic in various in vivo pain models. Administration of COE attenuated hypersensitivity in all postoperative, neuropathic, and menopausal pain models. Decreased hyperalgesia was confirmed by a mechanical withdrawal threshold assay and ultrasonic vocalization call analysis. In addition, application of COE inhibited the induction of the proinflammatory cytokines and calpain-3 on dorsal root ganglion neurons in a spared nerve injury rat model. Treatment with ferulic acid, which was identified as one of the components of COE by HPLC analysis, alleviated nociceptive behaviors. Our findings suggest that ferulic acid is an active compound from COE, and COE is a potential phytomedical source for pain relief by inhibiting the process of inflammation.