Short-Term Adjuvant Therapy with Terminalia arjuna Attenuates Ongoing Inflammation and Immune Imbalance in Patients with Stable Coronary Artery Disease: In Vitro and In Vivo Evidence

Kapoor, Divya; Trikha, D.; Vijayvergiya, Rajesh; Parashar, Kaustubh; Kaul, Deepak; Dhawan, Veena

doi:10.1007/s12265-015-9620-x

Cited by 11 publications

(8 citation statements)

References 40 publications

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“…Therefore, an alternative system of medicine like Ayurveda advocates the use of various medicinal plants, and one such plant is Terminalia arjuna (TA), which exhibits anti-inflammatory, anti-oxidant and hypolipidemic activities [5]. Consistent with this notion, our previous clinical trial data demonstrated that T.arjuna exhibits both anti-inflammatory and anti-atherosclerotic potential in patients with stable coronary artery disease, suggesting its cardio-protective role [6]. However, there is a dearth of information on anti-atherosclerotic therapeutic effect of the extracts obtained from these natural compounds, which can be employed for treating atherosclerosis by specifically targeting macrophages and foam cells in the initial stages of the lesion development.…”

Section: Introductionmentioning

confidence: 91%

Terminalia Arjuna bark extract impedes foam cell formation and promotes apoptosis in ox-LDL-stimulated macrophages by enhancing UPR-CHOP pathway

2019

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BackgroundIncreased macrophage and foam cell apoptosis during early atherogenesis retards plaque progression by impeding foam cell formation, suppressing inflammation and limiting lesion cellularity. Our previous in vitro study in THP1 macrophages demonstrated that Terminalia Arjuna (TA) attenuates dual-specificity phosphatase1 (DUSP1), a key negative regulator of JNK/P38MAPK signaling cascade, the branch also implicated in the UPR (unfolded protein response)-CHOP-mediated apoptotic pathway; however this pathway has not been explored so far in the presence of TA. Therefore, we aimed to elucidate the pro-apoptotic effect of aqueous bark extract of TA (aqTAE) on macrophage and foam cells and the underlying mechanism associated with it.MethodsTHP1 cells were initially differentiated into macrophages with phorbol-12-myristate-13-acetate (PMA) (100 ng/ml) for 24 h, followed by ox-LDL (100 μg/ml) treatment for another 24 h to induce foam cell formation. Thereafter, macrophages and ox-LDL- treated cells were incubated with aqTAE (100 μg/ml) for the next 24 h. Further, Oil Red O (ORO) staining, CD36 expression profiling, apoptotic assay and transcriptional and translational expression of ER-stress markers i.e., X-box binding protein 1 (XBP1) and C/EBP homologous protein (CHOP) were performed for elucidating the potential mechanism underlying TA-induced macrophage and foam cell apoptosis.ResultsWe demonstrated that ox-LDL treatment significantly increased lipid accumulation and upregulated CD36 expression, indicating foam cell formation; while the addition of aqTAE resulted in a significant decline in ORO positive cells, and suppression of CD36 expression in ox-LDL-stimulated macrophages, suggestive of reduced formation of lipid-laden foam cells. Further, aqTAE treatment alone and in combination with oxidized low-density lipoprotein (ox-LDL) stimulus, significantly attenuated CD36 expression; increased apoptosis; and augmented the expression of UPR regulatory proteins including XBP1 and CHOP, and similar observations were noted when cells were treated with ox-LDL alone. These findings indicate that TA promotes macrophage and foam cell apoptosis via enhancing UPR-mediated activation of JNK/p38MAPK-CHOP pathway in a DUSP1-dependent manner, implying a possible interplay between ox-LDL-induced ER stress- and TA-mediated MAPK signaling.ConclusionOur data shows that aqTAE inhibits foam cell formation, as well as promotes macrophage and foam cell apoptosis by augmenting UPR- JNK/p38MAPK-CHOP signaling cascade via inhibiting DUSP1. These findings provide novel mechanistic insight into the anti-atherogenic potential of TA, which may prove beneficial against early-stage atherosclerotic lesions.

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Section: Introductionmentioning

confidence: 91%

Terminalia Arjuna bark extract impedes foam cell formation and promotes apoptosis in ox-LDL-stimulated macrophages by enhancing UPR-CHOP pathway

2019

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“…Wight & Arn. showed immunomodulatory effect when used as adjuvant therapy in coronary artery disease and extracts and pectins from Terminalia macroptera Guill. & Perr.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of cytotoxic, immunomodulatory and antibacterial activities of aqueous extract from leaves ofConocarpus erectusLinnaeus (Combretaceae)

Santos

Almeida

Araújo

et al. 2018

Journal of Pharmacy and Pharmacology

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“…Wight & Arn. in patients with cardiovascular diseases ( Kapoor et al., 2015 ; Maulik et al., 2016 ; Priya et al., 2019 ). The report of Priya et al.…”

Section: Preclinical and Clinical Studies On Active Compounds From mentioning

confidence: 99%

Plants of the Genus Terminalia: An Insight on Its Biological Potentials, Pre-Clinical and Clinical Studies

et al. 2020

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The evaluation and confirmation of healing properties of several plant species of genus Terminalia based on their traditional uses and the clinical claims are of utmost importance. Genus Terminalia has received more attention to assess and validate the therapeutic potential and clinical approval due to its immense folk medicinal and traditional applications. Various species of Terminalia genus are used in the form of herbal medicine and formulations, in treatment of diseases, including headache, fever, pneumonia, flu, geriatric, cancer, to improve memory, abdominal and back pain, cough and cold, conjunctivitis, diarrhea, heart disorder, leprosy, sexually transmitted diseases, and urinary tract disorders. These are reported to possess numerous biological properties, counting: antibacterial, antifungal, antiinflammatory, antiviral, antiretroviral, antioxidant, and antipa7rasitic. This current research review aims to update the detailed biological activities, pre-clinical and clinical studies of various extracts and secondary metabolites from several plant species under the genus Terminalia , along with information on the traditional uses and chemical composition to develop a promising strategy for their potential applications in the form of medicine or use in modern drug formulations for treating diseases like pneumonia, flu, and other types of viral infections or controlling human contagions.

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Short-Term Adjuvant Therapy with Terminalia arjuna Attenuates Ongoing Inflammation and Immune Imbalance in Patients with Stable Coronary Artery Disease: In Vitro and In Vivo Evidence

Cited by 11 publications

References 40 publications

Terminalia Arjuna bark extract impedes foam cell formation and promotes apoptosis in ox-LDL-stimulated macrophages by enhancing UPR-CHOP pathway

Terminalia Arjuna bark extract impedes foam cell formation and promotes apoptosis in ox-LDL-stimulated macrophages by enhancing UPR-CHOP pathway

Evaluation of cytotoxic, immunomodulatory and antibacterial activities of aqueous extract from leaves ofConocarpus erectusLinnaeus (Combretaceae)

Plants of the Genus Terminalia: An Insight on Its Biological Potentials, Pre-Clinical and Clinical Studies

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