Citrus unshiu peel extract alleviates cancer-induced weight loss in mice bearing CT-26 adenocarcinoma

Abstract

Skeletal muscle atrophy is a critical feature of cancer-induced cachexia, caused by pro-cachectic factors secreted by host cells and tumor cells. Therefore, blockade of these factors has considered a reasonable target for pharmacological and nutritional interventions to prevent skeletal muscle loss under cancer-induced cachexia. Citrus unshiu peel (CUP) has been used for treating the common cold, dyspepsia, and bronchial discomfort and reported to have pharmacological activities against inflammation, allergy, diabetes, and viral infection. In the present study, we observed that daily oral administration of water extract of CUP (WCUP) to male BALB/c mice bearing CT-26 adenocarcinoma remarkably reduced the losses in final body weight, carcass weight, gastrocnemius muscle, epididymal adipose tissue, and hemoglobin (Hb), compared with saline treatment. The levels of serum IL-6 and muscle-specific E3 ligases elevated by tumor burden were also considerably reduced by WCUP administration. In an in vitro experiment, WCUP efficiently suppressed the production of pro-cachectic cytokines in immune cells as well as cancer cells. In addition, WCUP treatment attenuated C2C12 skeletal muscle cell atrophy caused by cancer cells. These findings collectively suggest that WCUP is beneficial as a nutritional supplement for the management of cancer patients with severe weight loss.

Japanese Herbal Medicine Ninjinyoeito Mediates Its Orexigenic Properties Partially by Activating Orexin 1 Receptors

“…In this study, we revealed that NYT and citrus unshiu peel activated OX1R using an in vitro assay. Kim et al have shown that citrus unshiu peel extract alleviates cancerinduced weight loss in mice bearing CT-26 adenocarcinoma (60). Although further studies using cancer cachexia-anorexia model animals are required, these previous and our present data suggest that NYT might improve cancer cachexia-anorexia via the activation of OX1R.…”

Induction of apoptosis by ethanol extract of <i>Citrus unshiu</i> Markovich peel in human bladder cancer T24 cells through ROS-mediated inactivation of the PI3K/Akt pathway

“…Recently, while the possibility of anti-cancer activity of C. unshiu peel extract based on the increase of immune activity and anti-inflammatory effect has been raised (31,32), little research has been performed on the mechanism of cancer cell proliferation inhibition. In this study, it was demonstrated that EECU treatment induces the apoptosis of human bladder cancer T24 cells.…”

“…A study on a tumor-bearing mouse model has shown that C. unshiu peel (Chimpi) extract inhibits tumor growth, which was associated with an increased production of cytokines such as interferon-γ and tumor necrosis factor-α (31). In addition, Kim et al (32) reported that C. unshiu peel reduces systemic inflammation in tumor-bearing mice and inhibits the production of pro-cacheche factors in tumors with the prevention of skeletal muscle atrophy and weight loss. It has also been reported that polysaccharides or flavonoids found in the C. unshiu peel can inhibit the metastasis of cancer cells (33,34); however, the evidence for the therapeutic potentials of C. unshiu peel against human cancer cells and the molecular pathways involved in suppression of cancer cell apoptosis remain unclear.…”

Citrus Peel Extract Ameliorates High-Fat Diet-Induced NAFLD via Activation of AMPK Signaling

“…The previous researches have elucidated that several compounds of citrus plants possess a wide range of pharmacological effects, such as anti-inflammation, antioxidation, anticancer, and neuroprotection [1,2]. Specifically, the dried peel of citrus, a functional health food ingredient, is used as a traditional herbal ingredient to treat various digestive dysfunctions, involving dyspepsia, abdominal distension, and vomiting in East Asia [3]. Further, few in vivo studies on citrus extracts have indicated their ameliorative effects in disturbances of Nutrients 2020, 12, 673; doi:10.3390/nu12030673 www.mdpi.com/journal/nutrients gastrointestinal microbiota and obesity conditions.…”