Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

Ip, Fanny Chun Fun; Ng, Yu-Pong; Or, Terry Cho Tsun; Sun, Peiran; Fu, Guangmiao; Li, Jessica Y.H.; Ye, Wen‐Cai; Cheung, Tom H.; Ip, Nancy Y.

doi:10.1371/journal.pone.0182069

Cited by 19 publications

(11 citation statements)

References 59 publications

(78 reference statements)

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“…A study conducted by Ip et al (2017) found that anemoside A3 (AA3), a triterpenoid constituent of Pulsatilla chinensis (bai tou weng), inhibits T h 17 cell differentiation, and reduced both T h 1 and T h 17 inflammatory responses. While this study measured the immunomodulatory and neuroprotective effects of AA3 in MS, its findings elucidate the effects of AA3 on the immune system, and the mechanisms by which it may help restore homeostasis via the downregulation of these inflammatory cytokines (T h 1 and T h 17).…”

Section: Qingre (Formulas and Herbs That Clear Heat)mentioning

confidence: 99%

Chinese Herbal Medicine and Its Regulatory Effects on Tumor Related T Cells

Hoffman

et al. 2020

Front. Pharmacol.

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Traditional Chinese medicine is an accepted and integral part of clinical cancer management alongside Western medicine in China. However, historically TCM physicians were unaware of the chemical constituents of their formulations, and the specific biological targets in the body. Through HPLC, flow cytometry, and other processes, researchers now have a much clearer picture of how herbal medicine works in conjunction with the immune system in cancer therapy. Among them, the regulation of tumor-related T cells plays the most important role in modulating tumor immunity by traditional Chinese medicine. Encouraging results have been well-documented, including an increase in T cell production along with their associated cytokines, enhanced regulation of Tregs and important T cell ratios, the formation and function of Tregs in tumor microenvironments, and the promotion of the number and function of normal T Cells to reduce conventional cancer therapy side effects. Chinese herbal medicine represents a rich field of research from which to draw further inspiration for future studies. While promising agents have already been identified, the vast majority of Chinese herbal mechanisms remain undiscovered. In this review, we summarize the effects and mechanisms of specific Chinese herbs and herbal decoctions on tumor related T cells.

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Section: Qingre (Formulas and Herbs That Clear Heat)mentioning

confidence: 99%

Chinese Herbal Medicine and Its Regulatory Effects on Tumor Related T Cells

Hoffman

et al. 2020

Front. Pharmacol.

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“…Developing fast-acting antidepressants attracts considerable attention in the field of pharmacotherapies for depression. In the present study, we have shown that AA3, a triterpenoid saponin with pro-cognitive, neuroprotective and immunomodulatory properties (Ip et al, 2015, 2017; Gao et al, 2003), exhibited acute antidepressant-like effects in the mouse FST and TST, and was able to reverse chronic stress-triggered depression-like phenotypes in mice in a faster-onset manner than that of classical antidepressant. As to the potential mechanisms underlying AA3’s antidepressant-like actions, it was found that chronic stress-induced weakening of TA-CA1 excitatory neurotransmission and reduced expression of synaptic GluA2-lacking AMPAR in the SLM of mice could both be restored by AA3.…”

Section: Discussionmentioning

confidence: 69%

Anemoside A3 rapidly reverses depression-like behaviors and weakening of excitatory synaptic transmission in mouse models of depression

Wang

Lin

et al. 2018

J Psychopharmacol

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Background and aim: Developing fast-acting antidepressants attracts considerable attention. Anemoside A3, a natural triterpenoid glycoside isolated from Pulsatillae Radix, has been reported to produce antidepressant-like action in the forced swim test. We herein explore the fast-onset antidepressant-like potentials and antidepressant mechanisms of anemoside A3. Methods: The forced swim test and tail suspension test were used to determine the acute antidepressant-like action of anemoside A3. This action of anemoside A3 was confirmed in chronic mild stress and chronic social defeat stress models. In vitro extracellular field potential recordings were conducted to investigate the impact of anemoside A3 on chronic stress-induced alterations at temporoammonic-CA1 synapses. Western blot, whole-cell patch-clamp recordings, and microinjections of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonists into the stratum lacunosum-moleculare were performed to unravel the contribution of stratum lacunosum-moleculare α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors to anemoside A3’s antidepressant-like activity. In vivo microdialysis and pharmacological depletion of serotonin were implemented to examine the role of the serotonin system in the antidepressant-like effect of anemoside A3. Results: Anemoside A3 administered intraperitoneally displayed acute antidepressant-like effects in the mouse forced swim test and tail suspension test and anemoside A3 treatment (intraperitoneally) for five days was sufficient to reverse depression-related behaviors of mice subjected to chronic stress. Accordingly, chronic social defeat stress-induced weakening of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor-mediated neurotransmission in the temporoammonic-CA1 pathway and downregulation of synaptic GluA2-lacking α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor expression in the stratum lacunosum-moleculare could both be normalized by five days of anemoside A3 treatment (intraperitoneally). Moreover, intra-stratum lacunosum-moleculare infusion of GluA2-lacking α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist abolished anemoside A3’s antidepressant-like effect. Lastly, serotonin system was not implicated in anemoside A3’s antidepressant-like effect. Conclusions: Our results suggest that anemoside A3 induces a rapid antidepressant-like response by a stratum lacunosum-moleculare GluA2-lacking α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor-dependent mechanism. In view of this, anemoside A3 represents a promising agent for depression treatment.

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Section: Nature Productsmentioning

confidence: 99%

“…In mouse models, the mice were dosed with anemoside (AA3) at 30–300 mg/kg ( Ip et al, 2015 ; Ip et al, 2017 ; Wang C. et al, 2019 ). AA3 is usually administered intraperitoneally and orally ( Ip et al, 2015 ; Ip et al, 2017 ). AA3 is the primary effective component from pulsatilla ( Pulsatilla chinensis ), and it offers neuroprotection and ( Ip et al, 2015 ) inhibits inflammation via modulation of toll-like receptor 4 (TLR4)/myeloid differential protein-88 (MyD88) ( He et al, 2020 ).…”

Section: Nature Productsmentioning

confidence: 99%

“…AA3 is the primary effective component from pulsatilla ( Pulsatilla chinensis ), and it offers neuroprotection and ( Ip et al, 2015 ) inhibits inflammation via modulation of toll-like receptor 4 (TLR4)/myeloid differential protein-88 (MyD88) ( He et al, 2020 ). In addition, AA3 reduced the infiltration of inflammatory cells, regulated Th1 and Th17 cells, and decreased the expression of transcription factors STAT4 and STAT3 in the EAE model ( Ip et al, 2017 ). AA3, with anti-tumor, neuroprotective, and immunomodulatory effects, can be regarded as a possible drug for the treatment of neurodegenerative and autoimmune diseases ( Yoo and Park, 2012 ; Li et al, 2020c ).…”

Section: Nature Productsmentioning

confidence: 99%

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Role of Plant-Derived Natural Compounds in Experimental Autoimmune Encephalomyelitis: A Review of the Treatment Potential and Development Strategy

et al. 2021

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Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that is mainly mediated by pathological T-cells. Experimental autoimmune encephalomyelitis (EAE) is a well-known animal model of MS that is used to study the underlying mechanism and offers a theoretical basis for developing a novel therapy for MS. Good therapeutic effects have been observed after the administration of natural compounds and their derivatives as treatments for EAE. However, there has been a severe lag in the research and development of drug mechanisms related to MS. This review examines natural products that have the potential to effectively treat MS. The relevant data were consulted in order to elucidate the regulated mechanisms acting upon EAE by the flavonoids, glycosides, and triterpenoids derived from natural products. In addition, novel technologies such as network pharmacology, molecular docking, and high-throughput screening have been gradually applied in natural product development. The information provided herein can help improve targeting and timeliness for determining the specific mechanisms involved in natural medicine treatment and lay a foundation for further study.

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Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

Cited by 19 publications

References 59 publications

Chinese Herbal Medicine and Its Regulatory Effects on Tumor Related T Cells

Chinese Herbal Medicine and Its Regulatory Effects on Tumor Related T Cells

Anemoside A3 rapidly reverses depression-like behaviors and weakening of excitatory synaptic transmission in mouse models of depression

Role of Plant-Derived Natural Compounds in Experimental Autoimmune Encephalomyelitis: A Review of the Treatment Potential and Development Strategy

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