Effects Of Catalpol Research Articles

Catalpol inhibits HHcy-induced EndMT in endothelial cells by modulating ROS/NF-κB signaling

BackgroundHyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis (AS). Endothelial mesenchymal transition (EndMT) refers to the process in which endothelial cells lose endothelial cell morphology and characteristic gene expression, and acquire phenotypic characteristics and gene expression related to mesenchymal cells. Numerous studies have confirmed that EndMT is involved in the formation of atherosclerosis. Catalpol is one of the active components of Rehmannia, which has antioxidant, anti-inflammatory, anti-tumor, neuroprotective and other biological activities. Studies have shown that catalpol can reduce atherosclerotic plaque induced by high sugar or fat. However, the effect of catalpol on HHCY-induced EndMT is unclear.Methods and resultsIn vitro HHcy-treated primary human umbilical vein endothelial cells (HUVECs) were used to construct a cell model, and the antioxidants N-acetylcysteine (NAC) and catalase alcohol were administered. In vivo C57BL/6N mice were given a diet fed with 4.4% high methionine chow to construct a HHcy mice model and were treated with catalpol. The results showed that hhcy could induce morphological transformation of endothelial cells into mesenchymal cells, increase intracellular ROS content, up-regulate α-SMA, N-cadherin, p-p65 protein expression, down-regulate VE-cadherin, CD31 protein expression, induce pathological changes of aortic root endothelium, and increase aortic endothelial ROS content. Catalpol reversed these hhcy induced outcomes.ConclusionsCatalpol inhibits HHcy-induced EndMT, and the underlying mechanism may be related to the ROS/NF-κB signaling pathway. Catalpol may be a potential drug for the treatment of HHcy-related AS.

The Mechanism of Catalpol to Improve Oxidative Damage of Dermal Fibroblasts Based on Nrf2/HO-1 Signaling Pathway.

Catalpol, as a natural medicine small-molecule drug, has been proven to have anti-inflammatory and antioxidant pharmacological effects. The effect of catalpol on oxidative damage of mouse epidermal fibroblast L929 model and its mechanism were investigated by using hydrogen peroxide model, CCK8 method, flow cytometry, and Western blot. The effect of catalpol on Nrf2/HO-1 signaling pathway was further studied to improve oxidative stress in cell models. The results showed that catalpol had no cytotoxicity to L929 cells, and inhibited the apoptosis of L929 cells after oxidative damage in a concentration-dependent manner, thus playing a role in cell protection. The oxidative damage of cells was inhibited by up-regulating the expression of the signature protein of Nrf2/HO-1 signaling pathway and inhibiting the interstitial formation of cells. This study is a preliminary study on the protective function of catalpol against oxidation and apoptosis in dermal fibroblasts, which can provide a theoretical basis and drug guidance for promoting skin wound healing in the later stage.

Catalpol rescues LPS-induced cognitive impairment via inhibition of NF-Κb-regulated neuroinflammation and up-regulation of TrkB-mediated BDNF secretion in mice

Ethnopharmacological relevanceSeptic-associated encephalopathy (SAE) is a key manifestation of sepsis. Nevertheless, specific treatment for SAE is still lacking. Catalpol is an active component derived from Rehmanniae Radix, and has been demonstrated to be a potential neuroprotective agent. However, its effect on SAE still needs to be fully explored. AimTo address the benefits of catalpol on post-sepsis cognitive deterioration and related mechanisms. Materials and methodsNovel object recognition test, temporal order task, histopathology, and immunochemistry were applied to address the benefits of catalpol on LPS-triggered post-sepsis cognitive decline in mice. Xuebijing injection (10 ml/kg) has been utilized as a positive control in the above animal studies. After treatment, the catalpol content in the hippocampus was determined using LC-MS/MS. Finally, the mechanisms of catalpol were further assessed in BV2 and PC12 cells in vitro using Western blot, RT-PCR, flow cytometry, molecular docking tests, thermal shift assay, transmission electron microscopy, and immunofluorescence analysis. ResultsBehavior tests showed that catalpol therapy could lessen the cognitive impairment induced by LPS damage. HE, Nissl, immunofluorescence, transmission electron microscopy, and Golgi staining further reflected that catalpol treatment could restore lymphocyte infiltration, blood-brain barrier (BBB) degradation, and the decreasing complexity of dendritic trees. According to LC-MS/MS analysis, catalpol had a 136 ng/mg concentration in the hippocampus. In vitro investigation showed that catalpol could inhibit microglia M1 polarization via blocking NF-κB phosphorylation, translocation and then reducing inflammatory cytokine release in BV2 microglia cells. Brain-derived neurotrophic factor (BDNF) release up-regulation and TrkB pathway activation were observed in the catalpol treatment group in vivo and in vitro. The effect of catalpol on enhancing BDNF expression was inhibited by the specific inhibitor of TrkB (GNF-5837) in PC12 cells. Further molecular docking tests showed that catalpol formed weak hydrophobic bonds with TrkB. Besides, thermal shift assay also reflected that catalpol incubation caused a considerable change in the melting temperature of the TrkB. ConclusionCatalpol alleviates LPS-triggered post-sepsis cognitive impairment by reversing neuroinflammation via blocking the NF-κB pathway, up-regulating neurotrophic factors via the activation of TrkB pathway, and preserving BBB integrity.

Retraction Note: Effect of catalpol on remyelination through experimental autoimmune encephalomyelitis acting to promote Olig1 and Olig2 expressions in mice

Retraction Note: Effect of catalpol on remyelination through experimental autoimmune encephalomyelitis acting to promote Olig1 and Olig2 expressions in mice

Effects of Catalpol from Rehmannia glutinosa Extract on Skin Flaps.

Flaps are commonly used for repairing tissues and wounds in surgery. However, various factors can cause postoperative necrosis in these flaps. Catalpol is a bioactive component in extracts from Rehmannia glutinosa , which has pharmacologic characteristics that may improve flap survival. The experiments were performed in 36 male Sprague-Dawley rats divided into three groups: control, low-dose catalpol, and high-dose catalpol. The flap survival rate, neutrophil density, microvessel density, superoxide dismutase, and malondialdehyde levels were measured; histopathologic analysis was performed 7 days after surgery. Blood flow was measured by laser Doppler flowmetry and lead oxide-gelatin angiography. The levels of vascular endothelial growth factor, toll-like receptor 4, nuclear factor-kappa B, tumor necrosis factor-α, interleukin (IL)-6, nod-like receptor 3, cysteinyl aspartate specific proteinase-1 (caspase-1), IL-1β, and IL-18 were determined by immunohistochemistry. Catalpol treatment increased flap survival, reduced neutrophil recruitment and release, decreased malondialdehyde levels, and increased superoxide dismutase levels; thus, it effectively reduced oxidative stress, up-regulated the expression of vascular endothelial growth factor, and increased microvessel density. Laser Doppler flowmetry and lead oxide-gelatin angiography showed that catalpol treatment improved angiogenesis. Immunohistochemical analyses showed that catalpol inhibited the production of inflammatory factors, such as tumor necrosis factor-α and IL-6, by down-regulating toll-like receptor 4 and nuclear factor-κB. Furthermore, catalpol reduced cell pyroptosis by inhibiting the production of nod-like receptor 3 inflammasomes, thereby down-regulating the release of IL-1β and IL-18. Catalpol can improve the rate of flap survival. The research verified that the Rehmannia extract catalpol, through angiogenesis, inflammatory response, ischemia-reperfusion injury, and pyroptosis-related pathways, effectively improved the flap survival rate, which will provide new ideas for clinical medication.

Catalpol represses the migration, proliferation and epithelial mesenchymal transition of TGF β2 stimulated lens epithelial cells via TGF β/Smad and Notch1 signaling pathways

Purpose: To investigate the role of catalpol in posterior capsule opacification (PCO).
 Methods: Human lens epithelial cells (SRA01/04) were treated with TGF-β2 or co-treated with TGF-β2 and different concentrations of catalpol. Cell migration and viability were assessed via wound healing and CCK8, respectively. Epithelial- esenchymal transition and the underlying mechanism of action were evaluated using western blot.
 Results: Treatment with TGF-β2 significantly increased cell viability and promoted the migration of SRA01/04 (p < 0.001). However, catalpol significantly reduced cell viability and repressed the migration of TGF-β2-stimulated SRA01/04 (p < 0.001). Moreover, TGF-β2-stimulated increases in fibronectin, α-smooth muscle actin (α-SMA), snail and vimentin. Decreases of E-cadherin and connexin-43 in SRA01/04 were reversed by catalpol. Moreover, TGF-β2-stimulated the up-regulation of p-smad2/3, while SRA01/04 was down-regulated by catalpol, but attenuated TGF-β2-stimulated increases in Notch1 and Jagged1 in SRA01/04.
 Conclusion: Catalpol inhibits TGF-β2-stimulated migration, proliferation and epithelial- esenchymal transition of SRA01/04 through the inactivation of TGF-β/Smad and Notch1 signaling. Catalpol might be a novel preventive agent for PCO. However, the effect of catalpol on animal models of PCO should be investigated further.

The Impact of Catalpol on Proliferation, Apoptosis, Migration, and Oxidative Stress of Lung Cancer Cells Based on Nrf2/ARE Signaling.

The effects of catalpol on lung cancer cell proliferation, apoptosis, migration, and oxidative stress via the Nrf2/ARE signaling pathway are investigated in this work. Catalpol-12 g/mL group, catalpol-24 g/mL group, catalpol-48 g/mL group, catalpol − 48 g/mL + vector group, catalpol − 48 g/mL + Nrf2 group, si-NC group, and si-Nrf2 group were used to split lung cancer cells A549 into control groups. Proliferation was detected using the CCK-8 assay; apoptosis was detected using flow cytometry; migration was detected using the transwell chamber; ROS was distinguished using the DCFHDA method; MDA, SOD, and GSH were detected using the microvolume method; and Cleaved Caspase-3, Cleaved Caspase-9, Nrf2, HO-1, MMP-9, and MMP-2 were detected using the Western blot method. Catalpol 12 g/mL and 24 g/mL-48 g/mL treatment decreased the proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells when compared to the control group. SOD and GSH levels of lung cancer cells were decreased, and MDA and ROS levels were increased. Cleaved caspase-3, cleaved caspase-9 protein expression levels, and apoptosis were boosted (P < 0.05). The proliferation activity, migration number, and protein levels of Nrf2, HO-1, MMP-9, and MMP-2 in the catalpol − 48 g/mL + Nrf2 group were raised compared to the catalpol − 48 g/mL + vector group, whereas there was an apparent drop in the Cleaved Caspase-3, Cleaved Caspase-9, and apoptosis rate. Similarly, SOD and GSH contents increased, whereas MDA and ROS decreased (P < 0.05). The proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells in the si-Nrf2 group were all decreased when compared to the si-NC and control groups. Cleaved Caspase-3 and Cleaved Caspase-9 protein expression, on the other hand, increased as MDA and ROS levels were raised while SOD and GSH levels dropped (P < 0.05). It reveals that catalpol inhibits the Nrf2/ARE signaling pathway, which causes antiproliferation, migration, apoptosis, and oxidative stress in cancer cells of lungs. The rate of apoptosis was also lowered.

Catalpol modulating the crosstalking between mesenchymal stromal cells and macrophages via paracrine to enhance angiogenesis and osteogenesis

Due to the inflammatory responses associated with defect occurrence and materials implantation, immunoregulation has emerged as a promising strategy to enhance bone regeneration. It has been widely reported that a material could facilitate osteogenesis if it can guide macrophages to anti-inflammatory M2 phenotype, vice versa, a substrate will influence macrophage phenotype if it is osteoinductive. However, few studies have looked into the intercellular crosstalking directly. Herein, the compound catalpol was selected for its multiple functions to study the interactions between bone marrow mesenchymal stromal cells (BMSCs) and macrophages. This iridoid glucoside exhibits excellent anti-inflammatory and osteoinductive activities. The effects of catalpol on mediating M1/M2 polarization of macrophages, inhibiting osteoclast differentiation, promoting osteogenesis and angiogenesis were systematically investigated to correlate the biological responses of BMSCs and macrophages. To extend its in vivo application, the catalpol was then loaded onto an electrospun polylactide/gelatin composite fibrous mesh and subcutaneously implanted to evaluate the local inflammation and ectopic osteogenesis. The results revealed that the functions of catalpol displayed in modulating cellular behaviors are via cell paracrine to strengthen intercellular crosstalking, hence demonstrating that catalpol itself could serve as a promising bioactive stimulator for bone tissue engineering.

Effects of Catalpol on Alzheimer's Disease and Its Mechanisms.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by memory loss and cognitive dysfunction. With the increasing aging of the population, the incidence of AD and the number of patients are also increasing year by year, causing more and more heavy burdens to the family and society. Catalpol, an iridoid glycoside compound, is one of the main active components of Rehmannia glutinosa. At present, a large number of experimental studies in vivo and in vitro have confirmed that catalpol has antioxidant, anti-inflammatory, antiapoptotic, and other neuroprotective effects, and it plays a significant role in the prevention and treatment of AD, with very small side effects and high safety. Therefore, it may be an ideal drug for the treatment of AD. Based on this, the role and mechanism of catalpol in AD will be comprehensively reviewed in the following.

Catalpol Ameliorates Neurotoxicity in N2a/APP695swe Cells and APP/PS1 Transgenic Mice

Alzheimer's disease (AD) causes progressive decline of memory and cognitive deficits. Because of its complicated pathogenesis, the prevention and therapy of AD remain an enormous challenge. It has been reported that catalpol possessed neuroprotective effects against AD. However, the involved mechanism still needs to be intensively studied. Therefore, the effects of catalpol on N2a/APP695swe cells and APP/PS1 mice were identified in the current study. Catalpol could improve cytotoxicity according to CCK-8 assay and ameliorate cellular morphological changes in N2a/APP695swe cells. Neuronal structural damage in the hippocampal CA1 region of APP/PS1 AD mice was improved according to HE staining and immunohistochemistry of NeuN. Meanwhile, catalpol administration ameliorated cognitive deficits confirmed by behaviorperformance of APP/PS1 mice. Hoechst 33,342 staining and Annexin V-FITC/PI double staining demonstrated that catalpol could reduce apoptosis in N2a/APP695swe cells. Likewise, TUNEL staining also manifested that catalpol significantly reduced apoptosis in hippocampal CA1 region of APP/PS1 mice. Catalpol administration also could improve mitochondrial functions indicated by the ameliorative mitochondrial morphology, the decreased ROS generation, and the increased MMP in N2a/APP695swe cells. Subsequently, catalpol restrained oligomerization of Aβ1-42, verified by a reduced ThT fluorescence dose- and time-dependently. Additionally, both Aβ1-40 and Aβ1-42 aggregation were decreased in N2a/APP695swe cells and APP/PS1 mice administrated with catalpol confirmed by ELISA and western blot. Western blot also showed that catalpol facilitated the phosphorylation of AKT and GSK3β, and impeded the expression of BACE1 both in vivo and in vitro. Finally, a slight alteration in lactylation, 2-hydroxyisobutyrylation, and phosphorylation were found in N2a/APP695swe cells treated with catalpol. Together, these findings manifested that catalpol served a neuroprotective effect in AD and might be a novel and expecting prophylactic or curative candidate for AD or neurodegenerative diseases therapy.

Protective Effects of Catalpol on Limb Motor Function and Ultrastructure of Hippocampal Neurons in Rats with Cerebral Ischemia.

This study aimed to examine the protective effects of catalpa on ultrastructure of hippocampal neuron and limb motor function in rats with cerebral ischemia. 90 healthy Sprague-Dawley male rats were randomly divided into control (n = 30) and model (n = 60) groups. Cerebral ischemia and hippocampal neurons were induced by occluding the internal carotid artery and injection of high blood glucose, respectively. Model rats were randomly divided into routine (n = 30) and observational (n = 30) groups. Animals in the routine group received edaravone injection (7mg/kg/day) for 14days, while rats in the observation group were treated with catalpol (30mg/kg/day) for 14days. Limb motor function score, fine motion execution capability, number of hippocampal neurons retained, and the ultrastructure of hippocampal nerve cells were considered at 3, 7, and 14days after treatments. A significant difference was observed in the mean scores of limb motor function, fine motor execution ability, and the number of hippocampal neurons retained between groups (p < 0.001). Repetitive treatments with catalpol significantly improved the mean number of hippocampal neurons retained (p < 0.01), limb motor function (p < 0.001), and fine motor execution ability scores (p < 0.01) at 3, 7, and 14days compared to edaravone. Catalpol treatments also improved the ultrastructure morphology of neuronal cells. Catalpa can effectively improve limb motor function and protect hippocampal neuron function in rats with cerebral ischemia.

Catalpol Protects Against Pulmonary Fibrosis Through Inhibiting TGF-β1/Smad3 and Wnt/β-Catenin Signaling Pathways.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by fibroblast proliferation and extracellular matrix remodeling; however, the molecular mechanisms underlying its occurrence and development are not yet fully understood. Despite it having a variety of beneficial pharmacological activities, the effects of catalpol (CAT), which is extracted from Rehmannia glutinosa, in IPF are not known. In this study, the differentially expressed genes, proteins, and pathways of IPF in the Gene Expression Omnibus database were analyzed, and CAT was molecularly docked with the corresponding key proteins to screen its pharmacological targets, which were then verified using an animal model. The results show that collagen metabolism imbalance, inflammatory response, and epithelial-mesenchymal transition (EMT) are the core processes in IPF, and the TGF-β1/Smad3 and Wnt/β-catenin pathways are the key signaling pathways for the development of pulmonary fibrosis. Our results also suggest that CAT binds to TGF-βR1, Smad3, Wnt3a, and GSK-3β through hydrogen bonds, van der Waals bonds, and other interactions to downregulate the expression and phosphorylation of Smad3, Wnt3a, GSK-3β, and β-catenin, inhibit the expression of cytokines, and reduce the degree of oxidative stress in lung tissue. Furthermore, CAT can inhibit the EMT process and collagen remodeling by downregulating fibrotic biomarkers and promoting the expression of epithelial cadherin. This study elucidates several key processes and signaling pathways involved in the development of IPF, and suggests the potential value of CAT in the treatment of IPF.

Network Pharmacology-Based Prediction of Catalpol and Mechanisms against Stroke.

Aim To apply the network pharmacology method to screen the target of catalpol prevention and treatment of stroke, and explore the pharmacological mechanism of Catalpol prevention and treatment of stroke. Methods PharmMapper, GeneCards, DAVID, and other databases were used to find key targets. We selected hub protein and catalpol which were screened for molecular docking verification. Based on the results of molecular docking, the ITC was used to determine the binding coefficient between the highest scoring protein and catalpol. The GEO database and ROC curve were used to evaluate the correlation between key targets. Results 27 key targets were obtained by mapping the predicted catalpol-related targets to the disease. Hub genes (ALB, CASP3, MAPK1 (14), MMP9, ACE, KDR, etc.) were obtained in the key target PPI network. The results of KEGG enrichment analysis showed that its signal pathway was involved in angiogenic remodeling such as VEGF, neurotrophic factors, and inflammation. The results of molecular docking showed that ACE had the highest docking score. Therefore, the ITC was used for the titration of ACE and catalpol. The results showed that catalpol had a strong binding force with ACE. Conclusion Network pharmacology combined with molecular docking predicts key genes, proteins, and signaling pathways for catalpol in treating stroke. The strong binding force between catalpol and ACE was obtained by using ITC, and the results of molecular docking were verified to lay the foundation for further research on the effect of catalpol on ACE. ROC results showed that the AUC values of the key targets are all >0.5. This article uses network pharmacology to provide a reference for a more in-depth study of catalpol's mechanism and experimental design.

Catalpol-Induced AMPK Activation Alleviates Cisplatin-Induced Nephrotoxicity through the Mitochondrial-Dependent Pathway without Compromising Its Anticancer Properties.

Nephrotoxicity is a common complication of cisplatin chemotherapy and, thus, limits the clinical application of cisplatin. In this work, the effects of catalpol (CAT), a bioactive ingredient extracted from Rehmannia glutinosa, on cisplatin-induced nephrotoxicity and antitumor efficacy were comprehensively investigated. Specifically, the protective effect of CAT on cisplatin-induced injury was explored in mice and HK-2 cells. In vivo, CAT administration strikingly suppressed cisplatin-induced renal dysfunction, morphology damage, apoptosis, and inflammation. In vitro, CAT induced activation of adenosine 5′-monophosphate- (AMP-) activated protein kinase (AMPK), improved mitochondrial function, and decreased generation of cellular reactive oxygen species (ROS), leading to a reduction in inflammation and apoptosis, which ultimately protected from cisplatin-induced injury. However, the beneficial effects of CAT were mostly blocked by coincubation with compound C. Furthermore, molecular docking results indicated that CAT had a higher affinity for AMPK than other AMPK activators such as danthron, phenformin, and metformin. Importantly, CAT possessed the ability to reverse drug resistance without compromising the antitumor properties of cisplatin. These findings suggest that CAT exerts positive effects against cisplatin-induced renal injury through reversing drug resistance via the mitochondrial-dependent pathway without affecting the anticancer activity of cisplatin.

Catalpol‑mediated microRNA‑34a suppresses autophagy and malignancy by regulating SIRT1 in colorectal cancer.

Colorectal cancer (CRC) is one of the most common digestive tract tumors worldwide. Catalpol exerts inhibitory effects on the progression of several cancer types by regulating microRNAs (miRs). However, the precise role and carcinostatic mechanism of catalpol on CRC cells are poorly understood which limits the application of catalpol treatment. In the present study, miR-34a and sirtuin 1 (SIRT1) expression levels were detected in CRC tissues and CRC cell lines by RT-qPCR. Computational software analysis, luciferase assays and western blotting were used to demonstrate the downstream target of miR-34a in CRC cells. Effects of catalpol on cell viability, apoptosis, autophagic flux and the miR-34a/SIRT1 axis in the CRC cells were assessed by CCK-8 assay, flow cytometry, electron microscopy and western blotting, respectively. Whether the miR-34a/SIRT1 axis participated in catalpol-mediated autophagy and apoptosis was investigated. The effects of catalpol on the miR-34a/SIRT1 axis and malignant behavior were evaluated in a rat model of azoxymethane (AOM)-induced CRC. It was revealed that miR-34a expression levels were significantly decreased while SIRT1 was overexpressed in most of the CRC tissues and all the CRC cell lines. Clinically, a low level of miR-34a was correlated with poor clinicopathological characteristics in CRC patients. Catalpol reduced cell viability, suppressed autophagy, promoted apoptosis, and regulated the expression of SIRT1 by inducing miR-34a in vitro and in vivo. The autophagy-inhibiting effect of catalpol may be a mechanism to promote apoptosis of CRC cells. miR-34a mimic transfection resulted in autophagy-suppressive activity similar to that of catalpol, while the miR-34a inhibitor attenuated the antiautophagic effects of catalpol. In conclusion, miR-34a is involved in regulating catalpol-mediated autophagy and malignant behavior by directly inhibiting SIRT1 in CRC.

Catalpol Enhances Neurogenesis And Inhibits Apoptosis Of New Neurons Via BDNF, But Not The BDNF/Trkb Pathway.

BackgroundThe role of catalpol in brain neurogenesis and newborn neuron survival has not been previously determined in permanent middle cerebral artery occlusion (pMCAO).MethodsFifty-four rats were divided into 6 groups: pMCAO (model, n=9); sham operation (NS, n=9); catalpol treatment (5 mg/kg and 10 mg/kg subgroups, n=9 each); K252a (n=9); and K252a+catalpol 5 mg/kg (n=9) with stroke. The effects of catalpol on behavior, neurogenesis surrounding the infarction ipsilateral to pMCAO, and the expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) were evaluated. Vehicle or, K252a (i.p.), an inhibitor of TrkB phosphorylase.ResultsRepeated administration of catalpol reduced neurological deficits and significantly improved neurogenesis. Catalpol increased the number of newborn immature neurons, as determined by BrdU+-Nestin+ and BrdU+-Tuj-1+ staining, and downregulated cleaved caspase 3 in Tuj-1+ cells at day 7 following stroke. Moreover, catalpol increased the protein expression of Tuj-1, MAP2, and the Bcl-2/Bax ratio, as determined using Western blot. Catalpol also significantly increased brain levels of BDNF, but not TrkB, resulting in enhanced survival of newborn neurons via inhibition of apoptosis.ConclusionCatalpol may contribute to neurogenesis in infarcted brain regions and help promote the survival of newborn neurons by activating BDNF, but not BDNF/TrkB signaling.

Catalpol ameliorates type II collagen-induced arthritis in rats and inhibits LPS-stimulated inflammatory response in SW982 human synovial cells

Abstract Catalpol, an effective component of China's functional food Rehmannia glutinosa Libosch, has a wide range of pharmacological effects. However, it is unclear whether catalpol exhibits protective and therapeutic potential against rheumatoid arthritis. In this study, the effects of catalpol in rats with collagen II-induced arthritis (CIA) and in LPS-stimulated SW982 human synovial cells were investigated. Catalpol significantly reduced paw swelling and thickness in rats with CIA. Histopathology revealed that catalpol alleviated articular cartilage damage, infiltration of inflammatory cells and synovial hyperplasia. Catalpol also inhibited protein and mRNA levels of IL-6, IL-8 and MMP-1, and the expression of COX-2 and mPGEs-1 in LPS-stimulated SW982 cells. Furthermore, the phosphorylation levels of ERK, JNK, p65, IκBα and c-Jun were suppressed by catalpol. Taken together, these findings showed that catalpol had inhibitory effects against arthritis, which may be related to decreased production of pro-inflammatory mediators and suppression of the MAPK, NF-κB and AP-1 pathways.

Effects of catalpol on bronchial asthma and its relationship with cytokines.

An animal (BALB/c mice) model of catalpol associated with bronchial asthma in vivo was established, and the effects of catalpol and its relationship with cytokines were investigated. A total of 30 adult BALB/c mice were randomly divided into a positive control group, a model group, and a catalpol group, with 10 mice in each group. The lung function of mice, the cell count, and the cytokine concentrations in bronchoalveolar lavage fluid (BALF) were detected. The levels of cytokines [interleukin 4 (IL-4), interleukin 5 (IL5), and interferon gamma (IFN-γ)] in BALF were measured with enzyme-linked immunosorbent assay methods. The total number of cells in the BALF of the group treated with catalpol was significantly lower than the model group. After treatment with catalpol, the eosinophils and neutrophils of the mice were remarkably reduced compared with the model group. The malondialdehyde content in the lung tissue homogenate of the mice was also decreased in the catalpol group. The cytokines IL-5 and IL-4 exhibited a similar tendency: the concentrations of IL-4 and IL-5 for the catalpol group were dramatically decreased compared with the model group. However, the IFN-γ concentration for the catalpol group was higher than the model group. The results indicated that IL-5 may involve in the pathologic process of asthma-like IL-4, and an inflammatory reaction may still exist in the airway during the remission stage of asthma. The imbalances of the cytokine network might be an important molecular basis in the asthma pathogenesis. It is suggested that catalpol may be a potential drug for the clinical treatment of asthma.

Catalpol inhibits TGF-β1-induced epithelial-mesenchymal transition in human non-small-cell lung cancer cells through the inactivation of Smad2/3 and NF-κB signaling pathways.

Catalpol, one of the main active ingredients isolated from Rehmannia glutinosa, was reported to possess anticancer activity. However, the role of catalpol in transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human non-small-cell lung cancer (NSCLC) cells has not been elucidated. The objective of this study was to investigate the effect of catalpol on EMT in human NSCLC cells. Our results showed that catalpol significantly inhibited the TGF-β1-induced cell migration and invasion of A549 cells, as well as repressed matrix metalloproteinase (MMP)2 and MMP9 expression induced by TGF-β1 in A549 cells. In addition, catalpol markedly repressed the EMT process in A549 cells in response to TGF-β1. Furthermore, catalpol prevented the activation of Smad2/3 and nuclear factor κB (NF-κB) signaling pathways induced by TGF-β1 in A549 cells. In conclusion, these findings indicated that catalpol inhibits TGF-β1-induced EMT in human NSCLC cells through the inactivation of Smad2/3 and NF-κB signaling pathways. Thus, catalpol may be a promising agent for the treatment of NSCLC.

Therapeutic effect of catalpol on type 2 diabetic mice induced by STZ and high-fat diet and its possible mechanism

To explore the therapeutic effect and possible mechanism of catalpol on type 2 diabetic mice. Twenty-four C57/BL6 male mice were randomly divided into four groups—normal control group (CON, n = 6), diabetic model group (DM, n = 6), the lower dose catalpol treatment (80 mg/kg body weight) group (DM+L, n = 6), and the higher dose catalpol treatment (160 mg/kg body weight) group (DM+H, n = 6). Intraperitoneal glucose tolerance test was performed after 30 days of treatment. Fasting blood glucose (FBG), triglyceride (TG), and total cholesterol (TC) in serum were detected by full automatic biochemical instrument. Enzyme-linked immunosorbent assay was used to detect insulin levels in serum. Insulin resistance level was calculated by trapezoid rule. The morphological changes of pancreatic tissue were observed through HE staining. The protein levels of insulin receptor substrate 1 (IRS1) and glucose transporter type 4 (GLUT4) in the liver and muscle were measured by Western blot (WB). Compared with the DM group mice, the glucose tolerance and insulin resistance in the DM+H group and the DM+L group were improved, the levels of TG, TC, and FBG decreased (p < 0.01). The blood insulin levels were elevated in the DM+H group and the DM+L group (p < 0.01) and the insulin resistance level decreased (p < 0.01, p < 0.05). IRS1 and GLUT4 protein levels in the liver and muscle increased in the DM+H group and the DM+L group (p < 0.01, p < 0.05). Catalpol could be potential medicine to treat type 2 diabetes. Its therapeutic mechanism might be improving insulin-stimulated glucose uptake in the liver and muscle.