Anti-Tumor Drug Discovery Based on Natural Product β-Elemene: Anti-Tumor Mechanisms and Structural Modification

Abstract

Natural products are important sources for drug discovery, especially anti-tumor drugs. β-Elemene, the prominent active ingredient extract from the rhizome of Curcuma wenyujin, is a representative natural product with broad anti-tumor activities. The main molecular mechanism of β-elemene is to inhibit tumor growth and proliferation, induce apoptosis, inhibit tumor cell invasion and metastasis, enhance the sensitivity of chemoradiotherapy, regulate the immune system, and reverse multidrug resistance (MDR). Elemene oral emulsion and elemene injection were approved by the China Food and Drug Administration (CFDA) for the treatment of various cancers and bone metastasis in 1994. However, the lipophilicity and low bioavailability limit its application. To discover better β-elemene-derived anti-tumor drugs with satisfying drug-like properties, researchers have modified its structure under the premise of not damaging the basic scaffold structure. In this review, we comprehensively discuss and summarize the potential anti-tumor mechanisms and the progress of structural modifications of β-elemene.

β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression

“…β-elemene, an extract of the rhizome of Curcuma longa, has been shown in several studies to have broad antitumor activity. It could inhibit tumor growth and proliferation, induce apoptosis, and modulate immunity [ 30 , 31 , 32 ]. β-elemene also exerts anti-inflammatory effects by inhibiting CCl 4 -induced serum TNF-α and endotoxin in rats, and experimentally demonstrated that β-elemene attenuates liver fibrosis [ 33 ].…”

Houttuynia cordata Thunb: An Ethnopharmacological Review

“…In addition, the pharmacological studies of the compound in vitro and even in vivo are not evidence that it can be converted into a drug to play a therapeutic role. Structural modification based on effective natural ingredients is expected to help reduce toxicity and enhance therapeutic activity, such as the β-elemene component in the rhizome of Wenyujin has been approved by the China Food and Drug Administration (CFDA) to treat a variety of cancers ( Bai et al, 2021 ). Therefore, in research on the bioactive components of H. cordata , structural modification may be an aspect that needs to be paid attention to.…”

Second generation β-elemene nitric oxide derivatives with reasonable linkers: potential hybrids against malignant brain glioma

“…It exerts a good anti-tumour effect in the human body through comprehensive mechanisms, including inhibition of tumour cell growth and proliferation, apoptosis, blocking tumour cell invasion and metastasis, and immune system regulation. More importantly, in human clinical trials, β-elemene also enhances the sensitivitsy of chemotherapy or radiotherapy and reverses multidrug resistance (MDR) 7 , 9 , 12–15 . After years of experimentation and efforts, elemene oral emulsion (CFDA number H20010338) and elemene injection (CFDA number H10960114) developed by our research team was approved by the China Food and Drug Administration (CFDA) as broad-spectrum anti-tumour drugs in the 1990s 7 Figure 1 .…”

“…More importantly, in human clinical trials, β-elemene also enhances the sensitivitsy of chemotherapy or radiotherapy and reverses multidrug resistance (MDR) 7 , 9 , 12–15 . After years of experimentation and efforts, elemene oral emulsion (CFDA number H20010338) and elemene injection (CFDA number H10960114) developed by our research team was approved by the China Food and Drug Administration (CFDA) as broad-spectrum anti-tumour drugs in the 1990s 7 Figure 1 .…”