Ginsenoside Rh4 inhibits breast cancer growth through targeting histone deacetylase 2 to regulate immune microenvironment and apoptosis

Dong, Fangming; Liu, Qu; Duan, Zhiguang; He, Ying; Ma, Xiaoxuan; Fan, Daidi

doi:10.1016/j.bioorg.2023.106537

Cited by 9 publications

(7 citation statements)

References 59 publications

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“…One of its components, Rh4, has been identified as a rare ginsenoside with potential inhibitive effects on the development of various cancers [ 100 ]. Rh4 can inhibit the expression of PD-L1 by regulating HDAC2-mediated JAK/STAT in breast cancer cells [ 101 ]. In addition, a study of the binding of Rh4 and HDAC2 suggests a high binding affinity existing between Rh4 and HDAC2, indicating the potential of ginseng as a dietary intervention for BC patients [ 101 ].…”

Section: Discussionmentioning

confidence: 99%

Potential of Dietary HDAC2i in Breast Cancer Patients Receiving PD-1/PD-L1 Inhibitors

Wang,

Lu,

Ling

et al. 2023

Nutrients

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Breast cancer (BC) is a lethal malignancy with high morbidity and mortality but lacks effective treatments thus far. Despite the introduction of immune checkpoint inhibitors (ICIs) (including PD-1/PD-L1 inhibitors), durable and optimal clinical benefits still remain elusive for a considerable number of BC patients. To break through such a dilemma, novel ICI-based combination therapy has been explored for enhancing the therapeutic effect. Recent evidence has just pointed out that the HDAC2 inhibitor (HDAC2i), which has been proven to exhibit an anti-cancer effect, can act as a sensitizer for ICIs therapy. Simultaneously, dietary intervention, as a crucial supportive therapy, has been reported to provide ingredients containing HDAC2 inhibitory activity. Thus, the novel integration of dietary intervention with ICIs therapy may offer promising possibilities for improving treatment outcomes. In this study, we first conducted the differential expression and prognostic analyses of HDAC2 and BC patients using the GENT2 and Kaplan–Meier plotter platform. Then, we summarized the potential diet candidates for such an integrated therapeutic strategy. This article not only provides a whole new therapeutic strategy for an HDAC2i-containing diet combined with PD-1/PD-L1 inhibitors for BC treatment, but also aims to ignite enthusiasm for exploring this field.

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Section: Discussionmentioning

confidence: 99%

Potential of Dietary HDAC2i in Breast Cancer Patients Receiving PD-1/PD-L1 Inhibitors

Wang,

Lu,

Ling

et al. 2023

Nutrients

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“…However, their substantial side effects and limited efficacy pose challenges, particularly for patients with a short life expectancy (Bisserier et al, 2020). Ginsenoside, an isolated compound from ginseng, possesses a diverse range of pharmacological properties, including anti-inflammatory (Qu et al, 2019;, anticancer (Dong et al, 2023;Pu et al, 2023), and anti-fibrotic (Yan et al, 2021) effects. Studies have revealed that ginsenoside Rg3 hinders pulmonary fibrosis by impeding the nuclear localization of HIF-1α, thereby targeting hypoxia (Fu et al, 2021).…”

Section: Dicussionmentioning

confidence: 99%

Ginsenoside Rh4 alleviates idiopathic pulmonary fibrosis by enhancing the CXCL9–CXCR3 axis

Yao,

Qu,

Deng

et al. 2024

Food Frontiers

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Idiopathic pulmonary fibrosis (IPF), often likened to a “tumor‐like disease,” proves more lethal than several malignancies. Although prior studies have demonstrated the lung‐protective efficacy of ginsenosides, the precise mechanism underlying their alleviative effect on IPF remains elusive. In this study, we validated the efficacy of the ginsenoside Rh4 in alleviating IPF and delved into the underlying mechanisms. Our data showed that Rh4 intervention significantly reduced mortality and hydroxyproline (HYP) content in mice. It also alleviated the pathological process of IPF by ameliorating phenomena such as alveolar wall thickening induced by IPF. In addition, in vitro cellular experiments confirmed that ginsenoside Rh4 was effective in alleviating transforming growth factor‐β1‐induced IPF model. Further analysis showed that ginsenoside Rh4 significantly reduced collagen fiber production and deposition while inhibiting the coagulation cascade signaling pathway. In addition, ginsenoside Rh4 inhibited the epithelial‐mesenchymal transition(EMT) pathway by promoting the CXCR3‐CXCL9 axis, which ultimately alleviated IPF. In conclusion, our data strongly suggest that ginsenoside Rh4 has the potential to be an innovative prophylactic drug against IPF.

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“…The total protein of hepatic tissues was extracted using standard procedures [17]. Briefly, tissues were ground and lysed using RIPA lysis containing 1% PMSF for 20 min.…”

Section: Immunoblotting Analysismentioning

confidence: 99%

Protective Effect of Ginsenoside CK against Autoimmune Hepatitis Induced by Concanavalin A

Zhang,

Liu,

et al. 2023

Foods

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Ginsenoside CK, a kind of rare ginsenoside transformed from protopanaxadiol saponins extracted from the genus Panax, has been proven to possess favorable bioactivities such as anti-inflammatory, anti-cancer, anti-diabetes, and hepatoprotective effects. The current study is targeted to determine the effect of ginsenoside CK on hepatitis induced by concanavalin A (Con A). Mice were treated with different dosages of ginsenoside CK for 7 days, and Con A (15 mg/kg) was intravenously injected to induce autoimmune hepatitis (AIH) after the last administration. The results demonstrated that pretreatment with ginsenoside CK (40 mg/kg) could obviously ameliorate the increase in serum indicators related to liver function such as AST, ALT, and ALP, and hepatic lesions induced by Con A. Meanwhile, ginsenoside CK suppressed hepatocyte apoptosis, which was observed in pathological data, and immunoblotting results showed that the expression of Bax, Bcl-2, and other proteins was regulated by CK. Furthermore, the release of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and IL-6 in mice with AIH were lowered by the administration of 40 mg/kg of ginsenoside CK. Furthermore, ginsenoside CK elevated the gene expression of Nrf2 and Sirt1 and augmented downstream target genes such as HO-1. In addition, a significant inhibition effect of the TLR4/NF-κB signal was observed in 40 mg/kg CK-pretreated mice compared with the model group. To sum up, the results indicated that ginsenoside CK has a notable hepatoprotective effect against AIH by activating Sirt1/Nrf2 and suppressing the TLR4/NF-κB signaling pathway.

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Ginsenoside Rh4 inhibits breast cancer growth through targeting histone deacetylase 2 to regulate immune microenvironment and apoptosis

Cited by 9 publications

References 59 publications

Potential of Dietary HDAC2i in Breast Cancer Patients Receiving PD-1/PD-L1 Inhibitors

Potential of Dietary HDAC2i in Breast Cancer Patients Receiving PD-1/PD-L1 Inhibitors

Ginsenoside Rh4 alleviates idiopathic pulmonary fibrosis by enhancing the CXCL9–CXCR3 axis

Protective Effect of Ginsenoside CK against Autoimmune Hepatitis Induced by Concanavalin A

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