1.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
2.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
3.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
4.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
5.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
6.Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023
Hsu-Heng YEN ; Jia-Feng WU ; Horng-Yuan WANG ; Ting-An CHANG ; Chung-Hsin CHANG ; Chen-Wang CHANG ; Te-Hsin CHAO ; Jen-Wei CHOU ; Yenn-Hwei CHOU ; Chiao-Hsiung CHUANG ; Wen-Hung HSU ; Tzu-Chi HSU ; Tien-Yu HUANG ; Tsung-I HUNG ; Puo-Hsien LE ; Chun-Che LIN ; Chun-Chi LIN ; Ching-Pin LIN ; Jen-Kou LIN ; Wei-Chen LIN ; Yen-Hsuan NI ; Ming-Jium SHIEH ; I-Lun SHIH ; Chia-Tung SHUN ; Tzung-Jiun TSAI ; Cheng-Yi WANG ; Meng-Tzu WENG ; Jau-Min WONG ; Deng-Chyang WU ; Shu-Chen WEI
Intestinal Research 2024;22(3):213-249
Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.
7.Management of Crohn’s disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023
Jia-Feng WU ; Hsu-Heng YEN ; Horng-Yuan WANG ; Ting-An CHANG ; Chung-Hsin CHANG ; Chen-Wang CHANG ; Te-Hsin CHAO ; Jen-Wei CHOU ; Yenn-Hwei CHOU ; Chiao-Hsiung CHUANG ; Wen-Hung HSU ; Tzu-Chi HSU ; Tien-Yu HUANG ; Tsung-I HUNG ; Puo-Hsien LE ; Chun-Che LIN ; Chun-Chi LIN ; Ching-Pin LIN ; Jen-Kou LIN ; Wei-Chen LIN ; Yen-Hsuan NI ; Ming-Jium SHIEH ; I-Lun SHIH ; Chia-Tung SHUN ; Tzung-Jiun TSAI ; Cheng-Yi WANG ; Meng-Tzu WENG ; Jau-Min WONG ; Deng-Chyang WU ; Shu-Chen WEI
Intestinal Research 2024;22(3):250-285
Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.
8.Lipopolysaccharide-induced Autophagy Increases SOX2-positive Astrocytes While Decreasing Neuronal Differentiation in the Adult Hippocampus
Wen-Chung LIU ; Chih-Wei WU ; Mu-Hui FU ; You-Lin TAIN ; Chih-Kuang LIANG ; I-Chun CHEN ; Chun-Ying HUNG ; Yu-Chi LEE ; Kay L.H. WU
Experimental Neurobiology 2022;31(5):307-323
Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g -1 •hour -1 for 7 days) was intraperitoneally infused into male Sprague–Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100β-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2 + -Beclin 1 + and SOX2 + -S100β + cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.
9.Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis
Po-Yao HSU ; Yu-Ju WEI ; Jia-Jung LEE ; Sheng-Wen NIU ; Jiun-Chi HUANG ; Cheng-Ting HSU ; Tyng-Yuan JANG ; Ming-Lun YEH ; Ching-I HUANG ; Po-Cheng LIANG ; Yi-Hung LIN ; Ming-Yen HSIEH ; Meng-Hsuan HSIEH ; Szu-Chia CHEN ; Chia-Yen DAI ; Zu-Yau LIN ; Shinn-Cherng CHEN ; Jee-Fu HUANG ; Jer-Ming CHANG ; Shang-Jyh HWANG ; Wan-Long CHUANG ; Chung-Feng HUANG ; Yi-Wen CHIU ; Ming-Lung YU
Clinical and Molecular Hepatology 2021;27(1):186-196
Background/Aims:
Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population.
Methods:
The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.
Results:
Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10).
Conclusions
HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.
10.Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease.
Shu Chen WEI ; Ting An CHANG ; Te Hsin CHAO ; Jinn Shiun CHEN ; Jen Wei CHOU ; Yenn Hwei CHOU ; Chiao Hsiung CHUANG ; Wen Hung HSU ; Tien Yu HUANG ; Tzu Chi HSU ; Chun Chi LIN ; Hung Hsin LIN ; Jen Kou LIN ; Wei Chen LIN ; Yen Hsuan NI ; Ming Jium SHIEH ; I Lun SHIH ; Chia Tung SHUN ; Yuk Ming TSANG ; Cheng Yi WANG ; Horng Yuan WANG ; Meng Tzu WENG ; Deng Chyang WU ; Wen Chieh WU ; Hsu Heng YEN ; Jau Min WONG
Intestinal Research 2017;15(3):285-310
Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.
Adrenal Cortex Hormones
;
Asian Continental Ancestry Group
;
Biological Therapy
;
Consensus*
;
Crohn Disease*
;
Diagnosis
;
Disease Management
;
Expert Testimony
;
Gastrointestinal Tract
;
Hepatitis B virus
;
Humans
;
Incidence
;
Inflammatory Bowel Diseases*
;
Magnetic Resonance Imaging
;
Prevalence
;
Quality of Life
;
Taiwan*
;
Tuberculosis

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