An Optimized Two-Herb Chinese Food as Medicine Formula Reduces Cisplatin-Induced Nephrotoxicity in the Treatment of Lung Cancer in Mice.

Le Shi,Sheng Hu,Xiaohua Li,Biaobiao Luo,Waheed Akram,Shuang Dong,Xuebo Hu,Jiuliang Zhang,Xiangdong Hu,Yang Shu,Jun Wang

doi:10.3389/fphar.2022.827901

Abstract

Chemotherapy is considered a most effective way to treat cancer. However, it is very common that chemotherapy causes unbearable mental and physical side effects to cancer patients, which ultimately reduces the patients’ confidence of overcoming diseases and compromises the treatment of chemotherapy. Cisplatin (DDP), a widely used anticancer agent for various types of cancers, also damages nontumor cells and tissues, which are mostly related to the activation of the inflammation pathway. Previously, we have discovered a few rational formulas of food as medicine materials that reduced systemic inflammation in in vitro and in vivo models. Hence, this study reports the ability of an optimized traditional Chinese anti-inflammatory formulation capable of synergizing the antitumor effect of DDP in vitro and in vivo. More significantly, by formulation of two anti-inflammatory herbal medicine, the Chrysanthemum × morifolium (Ramat.) Hemsl [Asteraceae] and Lonicera japonica Thunb [Caprifoliaceae] with a mediator Glycyrrhiza uralensis Fisch. ex DC [Fabaceae], a best formula relieved the kidney damage imposed by DDP. Treatments of various combinations of major chemical components of the three herbs also exhibited a similar trend for lowering the DDP-induced nephrotoxicity; however, contrary to that of the formula of herbal extracts, all chemical formulas could not recover the body weight and food intake of the tumor-bearing mice treated by DDP. Our findings suggested that the therapeutic index of DDP-based chemotherapy was able to be improved by minimizing toxicities from the two-herb formula to inhibit the inflammation in mouse tumor models and DDP-induced acute kidney injury mouse models.

Highlights

Cancer is a major cause of sickness in humans, and cancer incidence overall has been increasing (Chen et al, 2016; Feng et al, 2019)
Platinum drugs have been the most extensively used for cancer treatment in the past 50 years (Sun et al, 2019)
DDPbased chemotherapy is commonly used in the treatment of lung cancer of the second and third stages (Masutani et al, 1996; Pignon et al, 2008; Kim et al, 2019)

Summary

Introduction

Cancer is a major cause of sickness in humans, and cancer incidence overall has been increasing (Chen et al, 2016; Feng et al, 2019). The mechanism of DDP-induced nephrotoxicity was studied for a few decades. Urine contains glucose and a small amount of protein This indicates that the proximal tubular function is damaged, and hypomagnesemia often occurs after repeated use of DDP (Santoso et al, 2003). The main mechanism of DDP is to bind with the DNA molecules of cancer cells to kill them. The pharmacodynamic mechanism of DDP occurs in the kidney cells. These anticancer mechanisms inevitably cause damage to the kidneys (Frezza et al, 2010). Other studies have shown that the increase of reactive oxygen species and the production of proinflammatory cytokines seem to play an important role in the DDP-induced nephrotoxicity (Kaeidi et al, 2013; Ju et al, 2014)

Methods

Results

Conclusion