Antitumor effects of Chinese herbal medicine compounds and their nano-formulations on regulating the immune system microenvironment

Abstract

Traditional Chinese medicine (TCM), including herbal medicine, acupuncture and meditation, has a wide range of applications in China. In recent years, herbal compounding and active ingredients have been used to control tumor growth, reduce suffering, improve quality of life, and prolong the life span of cancer patients. To reduce side effects, herbal medicine can be used in conjunction with radiotherapy and chemotherapy or can be used as an adjuvant to strengthen the immune effect of anticancer vaccines. In particular, in the immunosuppressed tumor microenvironment, herbal medicine can have antitumor effects by stimulating the immune response. This paper reviews the advances in research on antitumor immunomodulation in Chinese herbal medicine, including the regulation of the innate immune system, which includes macrophages, MDSCs, and natural killer cells, and the adaptive immune system, which includes CD4+ T cells, CD8+ T cells, and regulatory T cells (Tregs), to influence tumor-associated inflammation. In addition, a combination of active ingredients of herbal medicine and modern nanotechnology alter the tumor immune microenvironment. In recent years, immunological antitumor therapy in TCM has been applied on a reasonably large scale both nationally and internationally, and there is potential for further clinical expansion. Investigation of immune modulation mechanisms in Chinese herbal medicine will provide novel perspectives of how herbal medicine controls tumor growth and metastasis, which will contribute to the evolution of tumor research.MethodologyExperimental research between the years of 2012-2022, meta-analysis and reviews for the period 2002-2022 found on the Databases including PubMed, Embase, and the Cochrane database were used. The inclusion criteria were experimental research literature addressing the anti-tumor immunological effects of active ingredients and nanoparticles in Chinese herbal medicine. Exclusion criteria were articles that addressed Chinese herbal medicine and nano-formulations without discussing anti-tumor immunological effects in innate, adaptive immune cells, MDSCs, and nuclear factors.

Emerging Trends in Nano-Driven Immunotherapy for Treatment of Cancer

“…Several studies have shown that compounds such as emodin, anemoside A3, dihydroartemisinin, dihydroisotanshinone I, gastrodin, puerarin, ginkgolide B, salidroside, etc. that are present in different herbs used in traditional Chinese medicine have been shown to modulate immune cell responses in different cancer models both in vitro and in vivo [ 151 ].…”

“…Similarly, herbal formulations such as Biejiajian pill, Yupingfeng, Baiying extract, Shuangshen granules, Xiaoyaosan, Yi-yi-fu-zi-bai-jiang-san, etc. have also shown promising immunomodulatory effects that could be harnessed for cancer immunotherapy [ 151 ]. To overcome bioavailability and targeting issues, nanoparticle mediated delivery of these phytocompounds have also been attempted.…”

“…Several herbal polysaccharides have been investigated for their ability to activate immune response both in the free state, as well as in the encapsulated form [ 154 ]. Though the preliminary studies on these molecules and formulations show promise for cancer immunotherapy, there are concerns about their toxicity that need to be addressed through systematic studies [ 151 ].…”

Traditionelle Chinesische Medizin in der Onkologie: wissenschaftliche Evidenz und Leitlinien

“…Hinweise für direkte Antitumorwirkungen einzelner Arzneipflanzen finden sich immer wieder, überwiegend aus In-vitro-Studien und aus Tierversuchen [49]. Klinische Studien belegen bislang keine ausreichende Evidenz für den Einsatz von chinesischen Arzneipflanzen als Tumortherapie.…”

A comprehensive review of antitumor properties of Angelica species and their antitumor‐responsible constituents and the underlying molecular mechanisms involved in tumor inhibition

“…Worldwide, tumor is the first‐line cause of human deaths and produces serious financial constraint (Wu et al, 2019). The immune system of each individual is correlated with tumor development, and recently it has been revealed that herbal compounds with their active ingredients have been used to control tumor growth, improve quality of life, reduce suffering, and prolong the life span of cancer patients (Sun et al, 2022). For that reason, natural products have become the research focus as they have low toxicity, are reliable to use, and are easy to extract as they are generally available (Pratheeshkumar et al, 2012).…”