| Inhibitory effect of baicalin on bacillary loads. Bacterial CFUs were counted after baicalin treatment for 48 h. **p < 0.01, Data are shown as mean ± SD of three independent experiments. 

| Inhibitory effect of baicalin on bacillary loads. Bacterial CFUs were counted after baicalin treatment for 48 h. **p < 0.01, Data are shown as mean ± SD of three independent experiments. 

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Tuberculosis (TB) remains a leading killer worldwide among infectious diseases and the effective control of TB is still challenging. Autophagy is an intracellular self-digestion process which has been increasingly recognized as a major host immune defense mechanism against intracellular microorganisms like Mycobacterium tuberculosis (Mtb) and serve...

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... we have confirmed the induction effect of baicalin on autophagy (Figure 2), to assess the antibacterial effect of baicalin on Mtb, we performed the colony forming unit (CFU) counting assay. As shown in Figure 3, FIGURE 7 | Bacalin suppresses the PI3K/Akt/mTOR pathway but has no effect on the MAPK signaling in Raw264.7 cells. (A) Western blot analysis of mTOR, p-mTOR, Akt, and p-Akt expression in Raw264.7 cells. ...

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... Likewise, Autophagy-related proteins were also significantly up-regulated by BA treatment in macrophages [60]. And this autophagy activation effect was partially mediated by regulating PI3K-AKT-mTOR pathway [61]. It has been reported that autophagy could promote ABCA1-dependent cholesterol efflux via increasing the free cholesterol availability. ...
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Atherosclerosis (AS) is the most common causes of cardiovascular disease characterized by the formation of atherosclerotic plaques in the arterial wall, and it has become a dominant public health problem that seriously threaten people worldwide. Autophagy is a cellular self-catabolism process, which is critical to protect cellular homeostasis against harmful conditions. Emerging evidence suggest that dysregulated autophagy is involved in the development of AS. Therefore, pharmacological interventions have been developed to inhibit the AS via autophagy induction. Among various AS treating methods, herbal medicines and natural products have been applied as effective complementary and alternative medicines to ameliorate AS and its associated cardiovascular disease. Recently, mounting evidence revealed that natural bioactive compounds from herbs and natural products could induce autophagy to suppress the occurrence and development of AS, by promoting cholesterol efflux, reducing plaque inflammation, and inhibiting apoptosis or senescence. In the present review, we highlight recent findings regarding possible effects and molecular mechanism of natural compounds in autophagy-targeted mitigation of atherosclerosis, aiming to provide new potential therapeutic strategies for the atherosclerosis treatment preclinically and clinically.
... 1. pathogen elimination mechanism [6] 2. antigen presentation and inflammation regulation [6,7] 3. IL-1b secretion and, consequently inflammatory response limitation [6] 4. MFs polarization [6,[8][9][10] 5. potential immunomodulation target in regenerative medicine [11][12][13] Endothelial cells (ECs) ...
... It has been pointed out that the MFs-induced inflammation triggered OCs-genesis and bone loss; however, the conversion of the proinflammatory phenotype M1 toward the anti-inflammatory M2 phenotype seemed to initiate and improve bone repair [66]; therefore, the autophagy-mediated M1 toward M2 conversion should be considered crucial for bone regeneration and implant osseointegration. For instance, it has been shown that the nanomaterials-derived autophagy induction has triggered MFs conversion toward M2 phenotype, consequently improving osteogenesis [8]. Experimental data led researchers to the conclusion that IL-17 has initiated osteogenesis; however, excessive IL-17 production has resulted in increased RANKL secretion and OCs-genesis [9,10]; therefore, IL-17 is still considered unfavorable for bone regeneration, and consequently, for the implant osseointegration. ...
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Dental endo-osseous implants have become a widely used treatment for replacing missing teeth. Dental implants are placed into a surgically created osteotomy in alveolar bone, the healing of the soft tissue lesion and the osseointegration of the implant being key elements to long-term success. Autophagy is considered the major intracellular degradation system, playing important roles in various cellular processes involved in dental implant integration. The aim of this review is an exploration of autophagy roles in the main cell types involved in the healing and remodeling of soft tissue lesions and implant osseointegration, post-implant surgery. We have focused on the autophagy pathway in macrophages, endothelial cells; osteoclasts, osteoblasts; fibroblasts, myofibroblasts and keratinocytes. In macrophages, autophagy modulates innate and adaptive immune responses playing a key role in osteo-immunity. Autophagy induction in endothelial cells promotes apoptosis resistance, cell survival, and protection against oxidative stress damage. The autophagic machinery is also involved in transporting stromal vesicles containing mineralization-related factors to the extracellular matrix and regulating osteoblasts’ functions. Alveolar bone remodeling is achieved by immune cells differentiation into osteoclasts; autophagy plays an important and active role in this process. Autophagy downregulation in fibroblasts induces apoptosis, leading to better wound healing by improving excessive deposition of extracellular matrix and inhibiting fibrosis progression. Autophagy seems to be a dual actor on the scene of dental implant surgery, imposing further research in order to completely reveal its positive features which may be essential for clinical efficacy.
... Thus, Rapamycin analogs such as Everolimus could represent a potential HDT in the treatment of Mtb [141]. Baicalin, a herbal medicine, and Nilotinib, a tyrosine kinase inhibitor, have been reported to trigger autophagy in Mtb-infected macrophages through the inhibition of PI3K/Akt/mTOR [142,143]. In human macrophages, the antichronic lymphocytic leukemia drug, ibrutinib, has been found to inhibit Mtb growth and promote auto-lysosome fusion by inhibiting the BTK/Akt/mTOR pathway [144]. ...
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Autophagy is a highly conserved dynamic process by which cells target their content to lysosomes for degradation, thus ensuring cell homeostasis. In response to environmental stress, the induction of autophagy is crucial for cell survival. Dysregulation of this degradative process has been implicated in a wide range of pathologies, including lung diseases, representing a relevant potential target to clinical outcomes. During lung disease progression and infection, autophagy may exert both cellular protective and harmful effects. In this review, we will explore the implications of autophagy and its selective forms in several lung infections, such as SARS-CoV-2, Respiratory Syncytial Virus (RSV) and Mycobacterium tuberculosis (Mtb) infections, and different lung diseases, among them Cystic Fibrosis (CF), Chronic Obstructive Pulmonary Disease (COPD) and Malignant Mesothelioma (MM).
... Mouse macrophage-like cell line Raw264.7 was obtained from ATCC (Manassas, VA) and cultured in DMEM supplemented with 10% fetal bovine serum (FBS) in 5% CO 2 at 37°C as described previously [43]. Thioglycolateelicited mouse primary peritoneal macrophages were prepared from male C57BL/6J mice (6-8 weeks of age) as described previously [44]. ...
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Tuberculosis (TB) remains a leading threat to public health worldwide with Mycobacterium tuberculosis (Mtb) infections causing long-term abnormal and excessive inflammatory responses, which in turn lead to lung damage and fibrosis, and ultimately death. Host-directed therapy (HDT) has been shown to be an effective anti-TB strategy in the absence of effective anti-TB drugs. Here, we used an in vitro macrophage model of Mtb infection to evaluate the effects of andrographolide (Andro), extracted from Andrographis paniculata, on pyroptosis in Mtb-infected macrophages. We evaluated the molecular mechanisms underlying these outcomes. These evaluations revealed that Andro downregulated the expression of proinflammatory miR-155-5p, which then promoted the expression of Nrf2 to suppress pyroptosis in Mtb-infected macrophages. Further study also demonstrated that siNrf2 could attenuate the inhibitory effect of Andro on TXNIP, validating our mechanistic studies. Thus, our data suggest that Andro may be a potential candidate adjuvant drug for anti-TB therapy as it inhibits pyroptosis in Mtb-infected macrophages, potentially improving clinical outcomes.
... Our study shows that baicalin-induced autophagy reduced the clinical aGVHD score in mice, mirroring these results. Another study showed that baicalin can induce autophagy through the PI3K/Akt/mTOR pathway, resulting in an anti-inflammatory effect 22 , which was confirmed in this study. ...
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Acute graft-versus-host disease (aGVHD) is the main complication of and cause of death after allogeneic hematopoietic stem cell transplantation. Baicalin can protect the small intestinal epithelial cells of rats against TNF-α-induced injury and alleviate enteritis-related diarrhea. To verify whether baicalin can protect the small intestinal mucosal barrier by regulating abnormal autophagy and interfering with intestinal aGVHD, a mouse model of aGVHD was established. CB6F1 micewere intravenously injected with a suspension of mononuclear cells derived from BALB/c donor mouse bone marrow and splenic tissue after treatment with 60Co X-rays. After treatment with different doses of baicalin for 15 days, the survival time, serum TNF-α and IL-10 levels, and autophagy markers levels in the intestine were assessed. A cell model of intestinal barrier dysfunction was also used to verify the effect of baicalin. The results showed that baicalin significantly prolonged the survival time, significantly reduced the aGVHD pathology score and clinical score by decreasing the TNF-α level with increasing the IL-10 level compared with the control. Transmission electron microscopy examination showed that baicalin treatment increased the number of autophagic vacuoles and led to the recovery of mitochondrial structures in the intestinal mucosal epithelial cells of mice and in Caco-2 cells. Western blotting results showed that baicalin treatment enhanced autophagy in vivo by regulating the AMPK/mTOR autophagy pathway. Similar results were observed in vitro in Caco-2 cells. Furthermore, the effect of baicalin was reduced after combination treatment with the autophagy inhibitor 3-methyladenine(3-MA). Baicalin can decrease the severity of small intestinal aGVHD by regulating autophagy by influencing imbalances in inflammatory cytokine levels and mucosal barrier damage, thus baicalin may have potential as a new treatment for aGVHD.
... Moreover, gardenoside and forsythin are defined as quality control indexes of XCQG in the Chinese Pharmacopoeia (9). Baicalin, honokiol, liquiritin, paeoniflorin and rhein are the major active compounds of SB, MO, GU, PL and RO, respectively, suggested to have anti-inflammatory (18,19), anti-influenza (20,21), antifungal and immunoregulatory functions (22). Although there are many previous literature on the compounds of these 14 herbals of XCQG, most of them probably use only one way of identifying compounds (23)(24)(25)(26)(27). ...
Article
The aim of this study was to establish a comprehensive strategy based on liquid chromatography coupled with mass spectrometry to potently identify as many compounds of Chinese patent medicine as possible. Ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to qualitatively analyze the Chinese patent medicine Xiao’er Chiqiao Qingre Granules (XCQG), which is recorded in the Chinese Pharmacopoeia. A novel strategy, including targeted, semi-targeted and non-targeted identification, was built to explore the compounds based on accurate mass, characteristic fragments, retention time of standard substances, databases or literature. Based on the integrated identification, 250 compounds were identified in total, including 7 alcohols, 3 aldehydes, 17 alkaloids, 9 amino acids, 10 coumarins, 30 flavonoids, 29 glycosides, 12 ketones, 7 lignans, 20 organic acids, 12 phenols, 11 phenylpropanoids, 9 quinones, 3 steroids, 26 terpenes, 14 volatile oils and 31 other compounds. A novel strategy for the identification of compounds in traditional Chinese medicine (TCM) was developed with Ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). It is also the first systematic study of compounds in XCQG, laying a foundation for further mechanism research of XCQG. More importantly, the strategy shows good application prospect in identifying compounds of TCM.
... Additional research showed that many signaling mechanisms of NLRP3 inflammasome activation are involved in diabetic complications. Zhang et al. (2017) found that autophagy can downregulate NLRP3 inflammasome via mammalian target of rapamycin (mTOR) signaling. Accordingly, Yang et al. (2019) reported that NLRP3 inflammasome can be inhibited by metformin and rapamycin (RAP, an mTOR inhibitor) by targeting the adenosine monophosphate-activated protein kinase (AMPK)/mTOR complex 1 (mTORC1)-dependent effects in diabetic cardiomyopathy. ...
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Background: Fucoidan (FPS) has been widely used to treat renal fibrosis (RF) in patients with diabetic kidney disease (DKD); however, the precise therapeutic mechanisms remain unclear. Recently, research focusing on inflammation-derived podocyte pyroptosis in DKD has attracted increasing attention. This phenomenon is mediated by the activation of the nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to RF during DKD progression. Therefore, we designed a series of experiments to investigate the ameliorative effects of FPS on RF in DKD and the mechanisms that are responsible for its effect on NLRP3 inflammasome-mediated podocyte pyroptosis in the diabetic kidney. Methods: The modified DKD rat models were subjected to uninephrectomy, intraperitoneal injection of streptozotocin, and a high-fat diet. Following induction of renal injury, the animals received either FPS, rapamycin (RAP), or a vehicle for 4 weeks. For in vitro research, we exposed murine podocytes to high glucose and MCC950, an NLRP3 inflammasome inhibitor, with or without FPS or RAP. Changes in the parameters related to RF and inflammatory podocyte injury were analyzed in vivo . Changes in podocyte pyroptosis, NLRP3 inflammasome activation, and activation of the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/NLRP3 signaling axis involved in these changes were analyzed in vivo and in vitro . Results: FPS and RAP ameliorated RF and inflammatory podocyte injury in the DKD model rats. Moreover, FPS and RAP attenuated podocyte pyroptosis, inhibited NLRP3 inflammasome activation, and regulated the AMPK/mTORC1/NLRP3 signaling axis in vivo and in vitro . Notably, our data showed that the regulative effects of FPS, both in vivo and in vitro , on the key signaling molecules, such as p-AMPK and p-raptor, in the AMPK/mTORC1/NLRP3 signaling axis were superior to those of RAP, but similar to those of metformin, an AMPK agonist, in vitro . Conclusion: We confirmed that FPS, similar to RAP, can alleviate RF in DKD by inhibiting NLRP3 inflammasome-mediated podocyte pyroptosis via regulation of the AMPK/mTORC1/NLRP3 signaling axis in the diabetic kidney. Our findings provide an in-depth understanding of the pathogenesis of RF, which will aid in identifying precise targets that can be used for DKD treatment.
... In their study, Atg5 was not required in alveolar macrophages during Mtb infection but exerted a unique protective role by preventing PMNs (polymorphonuclear cells)-mediated immunopathology (Kimmey et al., 2015). Recently, researchers have found that treating innate immune cells with the herbal medicine baicalin or vitamin D3 in combination with benzyl butyrate can induce autophagy and control inflammation caused by Mtb infection, which was valuable attempt to treat Mtb infection pharmacologically (Zhang et al., 2017;Rekha et al., 2018). ...
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Inflammation is an essential immune response of the host against infections but is often over-activated, leading to a variety of disorders. Autophagy, a conserved degradation pathway, also protects cells by capturing intracellular pathogens that enter the cell and transporting them to the lysosome for clearance. Dysfunctional autophagy is often associated with uncontrolled inflammatory responses during infection. In recent years, more and more research has focused on the crosstalk between autophagy and inflammation. In this paper, we review the latest research advances in this field, hoping to gain insight into the mechanisms by which the body balances autophagy and inflammation in infections and how this mechanism can be used to fight infections better.
... Baicalin is a flavone glycoside and is reported to enhance autophagic flux and Mtb clearance in infected macrophages by inhibiting the PI3K/Akt/mTOR signaling pathway [184]. ...
Article
Introduction: Malaria and tuberculosis are highly infectious diseases declared a global health emergency by the World Health Organization, and together they account for more than 1.5 million deaths worldwide each year. In the case of both malaria and tuberculosis, emergence of multidrug resistance towards frontline drugs has been reported in the recent past. Therefore, an urgent need exists for the discovery and development of novel drugs or therapies to fight these diseases. Areas covered: We provide a detailed overview of major infection strategies, commonly used by both the parasite Plasmodium and by Mycobacterium tubercolosis (Mtb) during disease development. We also describe selected host-directed drugs which can be repurposed to treat both malaria and tuberculosis, and co-infections. Expert opinion: Investigation of common infection strategies used by both Plasmodium and Mtb, during the development of disease in humans, suggests that they are potential host targets for which to develop host-directed therapies. By taking advantage of these common infection strategies, there is a chance that a number of available drugs can be repurposed to fight both malaria and tuberculosis, and their co-infections.
... Our findings revealed that baicalin exerted pro-proliferative and anti-apoptotic effects on NMDA-treated RGCs, suggesting that baicalin mitigates NMDA-induced cell injury of RGCs. Baicalin has been reported to regulate autophagy via PI3K/AKT signaling pathway [42,43]. In this study, NMDA-induced the elevation in levels of LC3-II, Beclin-1, and ATG5 in RGCs was counteracted by baicalin, which indicated that baicalin inhibits autophagy of NMDAtreated RGCs. ...
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Glaucoma, characterized with progressive degeneration of retinal ganglion cells (RGCs), is the second frequently leading cause of sight loss in the word after cataract. Baicalin plays a protective role in age-related macular degeneration, retinopathy of prematurity, branch retinal vein occlusion, and ischemia-induced neurodegeneration in the retina. The present study aimed to investigate the role of baicalin in glaucoma. RGCs were stimulated with N-methyl-D-aspartate (NMDA) to mimic the in vitro model of glaucoma. A mouse model of glaucoma induced by chronic elevated intraocular pressure was also established. The apoptosis, oxidative stress, and autophagy of RGCs were detected by flow cytometry analysis, 2,7-dichlorodihydrofluorescein diacetate staining, and Western blotting, respectively. Retinal pathological changes were exhibited by hemotoxylin and eosin staining. Baicalin restrained the NMDA-induced cell apoptosis, autophagy, and oxidative stress of RGCs by activating the PI3K/AKT signaling in vitro. The elevated intraocular pressure-induced pathological changes in retinas of glaucoma mice were attenuated by baicalin. Moreover, the number of RGCs was significantly decreased in glaucoma mice, and then increased by baicalin treatment. Baicalin also inhibited autophagy and activated PI3K/AKT signaling in vivo. In conclusion, baicalin suppresses glaucoma pathogenesis by regulating the PI3K/AKT signaling in vitro and in vivo.