Research Progress in Anti-tumor Effects of Traditional Chinese Medicine and Its Extracts

Jingjing LIAO, Hong LEI, Liting LAI, Bing QING, Wen ZHONG*, Yunli TANG*

1. Guangxi University of Chinese Medicine, Nanning 530200, China; 2. Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530201, China

Abstract Traditional Chinese medicine and its extracts have received widespread attention due to their significant anti-tumor effects and low adverse reactions. Many traditional Chinese medicine and its extracts have been applied in clinical tumor treatment. In this paper, the research progress in anti-tumor effects of plant-based traditional Chinese medicine and its extracts, animal-based traditional Chinese medicine and its extracts, and traditional Chinese medicine compound is reviewed.

Key words Traditional Chinese medicine, Tumor, Anti-tumor mechanism

1 Introduction

Tumor is a major disease that threatens human health. In February of 2022, the National Cancer Center released China’s latest cancer reportIncidenceRateandMortalityofCancerinChinain 2016 on theJournaloftheNationalCancerCenter. The report indicated that there were over 4 million new cases of cancer and over 2 million new deaths from cancer in China in 2016. From this report, it can be seen that the overall incidence of malignant tumors continues to rise nationwide, but it is lower in rural areas than in urban areas. The crude incidence rate of cancer in China shows a significant upward trend. But with the adjustment of population age structure, the standardized mortality rate shows a downward trend[1]. Conventional tumor treatment includes surgery, radiotherapy, and chemotherapy. Although all three treatment methods can improve the survival time of patients, due to the significant toxic side effects of radiotherapy and chemotherapy, patients have received different types of treatment and may have some resistance to chemotherapy. How to develop safe and effective new anticancer drugs is currently an urgent problem to be solved. Traditional Chinese medicine is a precious resource accumulated in China for thousands of years, such as artemisinin antimalarial drugs, and traditional Chinese medicine for COVID-19, which has extensive clinical application value. In recent years, traditional Chinese medicine has been widely used internationally in the treatment of cancer[2]. In this paper, the application and mechanism of traditional Chinese medicine and its extracts in anti-tumor therapy are reviewed.

2 Anti tumor plant-based traditional Chinese medicine and extracts

2.1 GinsenosideGinseng is a perennial plant of Panax of Araliaceae, known as the "king of herbs", rich in saponins, polysaccharides, flavonoids and other active substances. Ginsenosides are an important class of bioactive substances that play an important role in anticancer activity among various bioactive substances[4]. In terms of anti-cancer, ginsenoside can block the growth of cancer cells through death receptors, mitochondria, endoplasmic reticulum and other signal pathways, thereby promoting apoptosis of cancer cells, and thus playing an anti-cancer role[5]. Ginsenoside Rg3 has significant anticancer effects, and could activate cancerous cells apoptosis induced by Caspase-3 and Caspace-9, inhibit extracellular regulatory protein kinase (ERK) and Akt signaling pathway, and activate mitochondrial apoptosis pathway[6]. Additionally, Rg3 could inhibit EMT induced by TGF-β1 and make matrix metalloproteinase 2 and p38 mitogen activate and protein kinase and Smad2 deactivate, thereby inhibiting invasion and metastasis of tumors and vascular endothelial growth factor. Ginsenoside Rh2 also has the above functions, and its mechanism of action is more comprehensive and complex[7].

2.2 ArtemisininArtemisinin is an active ingredient extract of annualArtemisiaannuaand is currently the most efficient drug for treating malaria[8]. Artemisinin and its derivatives also have certain antiviral and anti-tumor effects[9]. The research by YAOetal.[10]showed that artemisinin derivatives artesunate (ARS) and dihydroartemisinin (DHA) could decline the expression of phosphorylated intracellular signal transduction protein (Smad3) and transforming growth factor β1 (TGF-β1), making that TGF-β signal transduction is inhibited, and cancer related fibroblasts deactivate, which can inhibit tumor growth and metastasis.

2.3 ResveratrolResveratrol is a natural polyphenol plant antitoxin, which exists in peanuts, grapes and their seeds,Reynoutriajaponica, and is rich in content. It has many pharmacological effects, such as antioxidant, anti-inflammatory, anti-cancer, anti neuropathy, immune regulation,etc[11-12]. The research by YUANetal.[13]showed that resveratrol can significantly inhibit the expression of N-cadherin, phosphorylated AKT1, phosphorylated glycogen synthase kinase-3β and Snail protein in colorectal cancer cells. It can also regulate Akt/GSK-3 β/Snail signaling pathway, thereby reversing epithelial mesenchymal transition in tumor tissue and inhibiting tumor invasion and metastasis.

2.4SculellariabarbataS.barbatais perennial herb of Labiatae, and it has the functions of clearing heat and detoxifying, promoting blood circulation and resolving blood stasis, reducing swelling and diuresis, and various pharmacological effects such as anti-tumor, immune regulation, anti-inflammatory, antiviral,etc.Its main chemical components include flavonoids, diterpenoids, polysaccharides, volatile oils, organic acids, and trace elements[14-15]. The study found that almost all the chemical components ofS.barbatahave different degrees of anti-tumor effects[16].S.barbataflavonoids could decline the levels of CD163, CD206 and IL-10, block Toll like receptor 4/myeloid differentiation factor (MyD88)-NF-κB signal pathway, and affect polarization of macrophage M1 to M2 in the tumor microenvironment of endometrial carcinoma[17]. The research by Zhang Haifangetal.[18]showed that the volatile oil contained inS.barbatahas a significant inhibitory effect on the proliferation of human lymphoma cell U937 and human gastric adenocarcinoma cell AGS.

2.5 Herba HedyotidisHerba Hedyotidis is from dry whole grass ofOlden-landiadiffusa(Wilid.) Roxb., which belongs toHedyotis, Rubiaceae Juss. This plant is unique in China, mainly distributed in Guangxi, Fujian, and surrounding areas. It has a bitter and light taste, a cold nature, and belongs to the stomach, large intestine, and small intestine meridians. It has the functions of clearing heat and detoxifying, reducing swelling, and promoting diuresis and dehumidification. Additionally, it has various pharmacological activities such as anti-tumor, neuroprotection, anti-inflammatory and antibacterial, antioxidant and anti-aging, and enhancing immunity[19-20]. Herba Hedyotidis is a common medicinal herb in the compound treatment of anti-tumor, and has been widely used in various anti-tumor treatments such as digestive system tumors, reproductive system tumors, respiratory system tumors, and myeloma[19-20]. As a traditional Chinese medicine, Herba Hedyotidis is used in many classic prescriptions for cancer treatment in clinic.

2.6 BerberineBerberine is the main bioactive component ofCoptischinensis, and its functions include antibacterial, anti-inflammatory, antioxidant, anti diabetes, improving cardiovascular disease, anti-tumor,etc[21-22]. Due to the fact that the growth of tumor cells relies on a large amount of lipids, increased lipid metabolism represents malignant tumors. In colon cancer cells DLD1 and Caco-1, LIUetal.[23]found that berberine can down regulate the expression of binding protein of cholesterol regulatory element and SREBP cleavage activating protein, and then regulate the expression of downstream fatty acid synthase, including fatty acid synthase, ATP citrate lyase, acetyl-CoA carboxylase, inhibit the lipid synthesis of tumor cells, and make Wnt/ β-catenin pathway inactivated. The cell cycle is blocked in G0/G1phase, and the proliferation of colon cancer cells is inhibited.

3 Anti tumor animal-based traditional Chinese medicine and extracts

3.1 CinobufotalinCinobufotalin is water soluble extract of the skin fromBufogargarizansorBufomelanostictusschneider through water alcohol method, and its components include toad dienolactones, alkaloids, peptides, toad cyclic amides, amino acids,etc[24]. Huachansu is a modern Chinese medicine injection developed based on the traditional Chinese medicine Bufonis Venenum, and belongs to the national protected variety of traditional Chinese medicine. It has the effects of clearing heat and detoxification, reducing swelling and relieving pain, dispelling blood stasis and dispersing nodules, and can be used to treat various malignant tumors, chronic hepatitis B and other diseases clinically[25]. Clinically, cinobufotalin has a very good anti-cancer effect. It can be used alone or in combination with chemotherapy and radiotherapy. It can effectively inhibit the growth and metastasis of tumors, and improve the symptoms related to cancer[26-27], especially for primary liver cancer, gastric cancer, pancreatic cancer, non-small cell lung cancer and other diseases. Cinobufotalin has a wide spectrum of anticancer, with less toxic side effects compared to chemotherapy drugs, and could enhance human immune function. Especially in clinical practice, cinobufotalin can significantly alleviate various tumor related pain, pain caused by tumors such as gastrointestinal tumors, lung cancer, and bone metastasis, and its total effective rate can reach 50%-97%. It greatly improves the quality of life of patients with advanced tumors[28], and demonstrates its unique advantages in clinical practice.

4 TCM compound

5 Conclusions

With the development of social economy, the incidence rate of tumors has been increasing year by year in recent years. At present, surgery, radiotherapy, chemotherapy,etc.are still the main treatment methods for cancer in clinical practice. However, the efficacy of traditional Chinese medicine has been recognized by both clinical practice and patients. With in-depth research on its mechanisms, the role of traditional Chinese medicine in cancer treatment is gradually becoming known. The therapeutic effects of traditional Chinese medicine on different biological levels of tumor tissue are not independent, but interrelated and interactive. It is precisely these interrelated effects that enable them to exert different therapeutic effects on tumor cells. Although traditional Chinese medicine has the advantages of high efficacy and no side effects in treatment, it is currently not feasible to independently apply traditional Chinese medicine to the treatment of cancer in clinical practice. Moreover, based on the research level of traditional Chinese medicine at home and abroad, it is indeed unable to achieve the effect of independently treating tumors.