Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis

Wang, Li; Wu, Tong; Si, Chunying; Wang, He; Ke, Yanxiong; Shang, Shasha; Li, Xiaohui; Chen, Yu‐Shan; Huaimin, Guan

doi:10.3389/fphar.2021.730525

Cited by 10 publications

(7 citation statements)

References 45 publications

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“…A previous study reported that the AKT/mTOR signaling pathway promoted the cellular activities of fibroblasts; notably, after intervening with LY294002 (an inhibitor of the AKT/mTOR signaling pathway), cellular viability and proliferation were reduced (3). Previous studies have also confirmed the inhibitory effect of AKT/mTOR signaling inactivation on fibroblast migration; notably, applying Morin (an anti-arthritis compound) has been shown to reduce the migration of fibroblasts in rheumatoid arthritis (56) and Danlou tablet (a Chinese medicine used to treat cardiovascular diseases) has been reported to restrain the migration of vascular adventitial fibroblasts in atherosclerosis (57). Furthermore, Lu et al revealed that an antibody against programmed cell death ligand 1 could inhibit fibroblast proliferation, migration and ECM deposition in pulmonary fibrosis through regulating the AKT/mTOR signaling pathway (58).…”

Section: Discussionmentioning

confidence: 87%

Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms

et al. 2022

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Excessive proliferation and migration of fibroblasts in the lumbar laminectomy area can lead to epidural fibrosis, eventually resulting in failed back surgery syndrome. It has been reported that laminin α1, a significant biofunctional glycoprotein in the extracellular matrix, is involved in several fibrosis-related diseases, such as pulmonary, liver and keloid fibrosis. However, the underlying mechanism of laminin α1 in epidural fibrosis remains unknown. The present study aimed to explore the effect and mechanism of laminin α1 in fibroblast proliferation, apoptosis and migration, and epidural fibrosis. Following the establishment of a laminectomy model, hematoxylin and eosin, Masson's trichrome and immunohistochemical staining were performed to determine the degree of epidural fibrosis, the number of fibroblasts, collagen content and the epidural expression levels of laminin α1, respectively. Furthermore, a stable small interfering RNA system was used to knock down the expression of laminin α1 in fibroblasts. The transfection efficiency was confirmed by reverse transcription-quantitative PCR and immunofluorescence staining. Western blot analysis, scratch wound assay, EdU incorporation assay, flow cytometric analysis and Cell Counting Kit 8 assay were performed to assess the proliferation, apoptosis, migration and viability of fibroblasts, as well as the expression levels of the AKT/mechanistic target of rapamycin (mTOR) signaling-related proteins. In vivo experiments revealed that laminin α1 was positively and time-dependently associated with epidural fibrosis. In addition, laminin α1 knockdown attenuated cell proliferation, viability and migration, and promoted apoptosis. Furthermore, the results revealed that the activation of the AKT/mTOR signaling pathway was involved in the aforementioned processes. Overall, the current study illustrated the positive association between laminin α1 and epidural fibrosis, and also verified the effect of laminin α1 on fibroblast proliferation, apoptosis and migration. Furthermore, the results suggested that the AKT/mTOR signaling pathway may serve a significant role in regulating the behavior of laminin α1-induced fibroblasts.

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Section: Discussionmentioning

confidence: 87%

Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms

et al. 2022

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“…The result of Oil Red O-staining showed that the lesion area was decreased in the CAP group when compared with the HFD group ( p < 0.01) ( Figure 1 B). The collagen levels in the aortic sinus were correlated with the stability of atherosclerotic plaques [ 17 ], and therefore we further evaluated the collagen levels by Masson’s trichrome staining. The results showed that the levels of collagen in the aortic sinus were increased in the CAP group when compared with the HFD group ( p < 0.01) ( Figure 1 C), indicating that capsaicin administration was beneficial for the stability of atherosclerotic plaques.…”

Section: Resultsmentioning

confidence: 99%

Capsaicin Ameliorates High-Fat Diet-Induced Atherosclerosis in ApoE−/− Mice via Remodeling Gut Microbiota

Dai

Meng

et al. 2022

Nutrients

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Capsaicin is a pungent alkaloid abundantly present in peppers with outstanding biological activities, including the anti-atherosclerosis effect. Previous studies revealed that gut microbiota played an important role in the beneficial effects of capsaicin, but whether it is essential for the anti-atherosclerosis effect of capsaicin is unclear. This study evaluated the anti-atherosclerosis effect of capsaicin in ApoE−/− mice and further explored the role of depleting gut microbiota in the improvement of atherosclerosis. The results showed that capsaicin administration could prevent the development of atherosclerosis and improve serum lipids and inflammation, while antibiotic intervention abolished the alleviation of atherosclerosis by capsaicin. In addition, capsaicin administration could significantly increase the abundance of Turicibacter, Odoribacter, and Ileibacterium in feces, and decrease the abundance of deoxycholic acid, cholic acid, hypoxanthine, and stercobilin in cecal content. Our study provides evidence that gut microbiota plays a critical role in the anti-atherosclerosis effect of capsaicin.

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“…DL comprises ten different types of botanical drugs such as Trichosanthes rosthornii Harms [Cucurbitaceae] and Allium macrostemon Bunge [Amaryllidaceae] with components primarily as artemisinolide (17.49%), β -Elemene (11.07%), and (-) Spartol (8.95%) ( Zhang et al, 2016 ). Studies of mechanism indicated that DL could inhibit NF-κB signaling, trigger PPARα/ABCA1 signaling pathway, and activate PI3K/Akt/mTOR-mediated autophagy of vascular adventitial fibroblasts, thus preventing atherosclerosis ( Hao et al, 2019 ; Wang L. et al, 2021 ). SXBX is composed of seven traditional Chinese medicines such as Panax ginseng C.A.Mey [Araliaceae], Cinnamomum verum J. Presl [Lauraceae], and Liquidambar orientalis Mill [Altingiaceae].…”

Section: Discussionmentioning

confidence: 99%

The comparative effects of oral Chinese patent medicines combined with western medicine in stable angina: A systematic review and network meta-analysis of 179 trials

Huang

Chen

et al. 2022

Front. Pharmacol.

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Background: Stable angina is a common condition with high morbidity and mortality rates. It has been reported that combining oral Chinese patent medicines (OCPMs) and Western medicine (WM) could potentially achieve a better effect than WM alone. However, the optimal OCPMs for stable angina remain controversial and merit further empirical research.Methods: PubMed, Embase, Web of Science, Cochrane Library, Ovid-Medline, Clinical Trials.gov, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database were all searched from inception to 13 March 2022. We employed Version 2 of the Cochrane risk-of-bias tool (ROB2) to assess the overall quality of the selected studies. We also used R 4.1.2 and STATA 14.0 software applications to perform network meta-analysis, followed by sensitivity and subgroup analysis.Results: A total of 179 randomized controlled trials with 16,789 patients were included. The selected trials were all assessed as some concerns. OCPMs combined with WM had a better treatment effect than WM alone. In terms of the effective clinical rate, a significant increase was detected for Qishen Yiqi dripping pill (QSYQ)+WM as compared with Shensong Yangxin capsule (SSYX)+WM, Shexiang Baoxin pill (SXBX)+WM, Tongxinluo capsule (TXL)+WM, Xuefu Zhuyu capsule (XFZY)+WM, Qiliqiangxin capsule (QLQX)+WM, Naoxintong capsule (NXT)+WM, Fufang Danshen dripping pill (FFDS)+WM, and Danlou tablet (DL)+WM. QSYQ + WM had the highest-ranking probability (98.12%). Regarding the effective rate in ECG, QSYQ + WM was superior to SXBX + WM, TXL + WM, DL + WM, FFDS + WM, and NXT + WM. QSYQ + WM ranked first (94.21%). In terms of weekly frequency of angina, QLQX + WM obtained a better effect than FFDS + WM, Kuanxiong aerosol (KXQW)+WM, NXT + WM, QLQX + WM, SSYX + WM, SXBX + WM, and TXL + WM. QLQX + WM ranked first (100.00%). Regarding the duration of an angina attack, KXQW + WM was superior to SSYX + WM; KXQW + WM ranked first (95.71%). Adverting to weekly nitroglycerin usage, TXL + WM had the highest-ranking probability (82.12%). Referring to cardiovascular event rate, DL + WM had the highest effect (73.94%). Additionally, SSYX + WM had the lowest rate of adverse drug reactions (1.14%).Conclusion: OCPMs combined with WM had a higher efficacy. QSYQ + WM, QLQX + WM, KXQW + WM, TXL + WM, DL + WM, SSYX + WM, and SXBX + WM merit further investigation. SXBX + WM is presumably the optimal treatment prescription for both clinically effective and cardiovascular event rates. Further high-quality empirical research is needed to confirm the current results.Systematic Review Registration: URL = https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316534, CRD 42022316534

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Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis

Cited by 10 publications

References 45 publications

Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms

Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms

Capsaicin Ameliorates High-Fat Diet-Induced Atherosclerosis in ApoE−/− Mice via Remodeling Gut Microbiota

The comparative effects of oral Chinese patent medicines combined with western medicine in stable angina: A systematic review and network meta-analysis of 179 trials

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