Antitumor and immunomodulatory activities of total flavonoids extract from persimmon leaves in H22 liver tumor-bearing mice

Shimei Zhao,Mengliang Zhang,Xiangyun Gao,Yutong Gao,Ying Gao,Li Chen,Xiaoting Yan,Anwen Zhang,Jinxia Li,Yundong Wei

doi:10.1038/s41598-018-28440-8

Abstract

Persimmon (Diospyros kaki L.) leaves are commonly used in Asia as tea infusion and as an agent in traditional medicine. The present study aims to explore the antitumor and immunomodulatory effects of total flavonoids extract from persimmon leaves (PLF) in H22 liver tumor-bearing mice. We found that the PLF showed significant inhibition on the liver tumor growth in mice with a tumor inhibition rate of up to 49.35%. In contrast to the severe side effects of cyclophosphamide (CTX), the PLF exhibited anti-cachexia effect and showed no alternation in the body weight and food intake in mice. Moreover, compared with the vehicle control and CTX group, the PLF significantly enhanced the thymus and spleen indices, level of serum interleukin-18 (IL-18), monocyte/macrophage phagocytosis, level of serum hemolysin, and activity of natural killer (NK) cells. This study demonstrated that the PLF could effectively inhibit liver tumor growth in vivo via enhancement of the immune function in mice, and it displayed the potential to be a safe and effective anticancer agent or functional immune-enhancing agent.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in humans
This study aims to investigate the in vivo antitumor and immunomodulatory effects of the PLF using an hepatoma 22 ascitic tumor (H22) tumor-bearing mice model, and provide a theoretical foundation for the development of PLF as a potential immunomodulatory agent that can help to reverse the immune deficiency on cancer patients
Persimmon leaves are known to contain high levels of flavone and flavonol glycosides, which have characteristic UV-Vis absorbance at around 354 nm19; 354 nm was used as the main acquisition wavelength in the UHPLC-PDA analysis

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in humans. The mortality rate of HCC is exceeded only by that of gastric cancer and lung cancer, making it the third leading cause of cancer death worldwide[1,2]. Current chemotherapeutic agents used to treat HCC mainly focus on attacking and killing the rapidly proliferating liver cancer cells and often overlook the impact on the body’s immune response. Accumulating clinical and experimental studies have shown that most cancer patients suffer from suppressed immune function coincident with the proliferation of cancer cells These studies demonstrate that the administration of chemotherapeutic agents aggravates the damage on the immune function resulting in serious adverse effects[4]. Previous studies have reported that a herbal prescription and plant-derived polysaccharides enhanced the body’s immune function while inhibiting tumor growth via promoting the proliferation of immune cells, accelerating the phagocytosis of macrophages, and regulating the production of cytokines[6,7]. This study aims to investigate the in vivo antitumor and immunomodulatory effects of the PLF using an H22 tumor-bearing mice model, and provide a theoretical foundation for the development of PLF as a potential immunomodulatory agent that can help to reverse the immune deficiency on cancer patients

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