Atractylenolides, essential components of Atractylodes-based traditional herbal medicines: Antioxidant, anti-inflammatory and anticancer properties

The rhizome of the plant Atractylodes macrocephala Koidz is the major constituent of the Traditional Chinese Medicine Baizhu, frequently used to treat gastro-intestinal diseases. Many traditional medicine prescriptions based on Baizhu and the similar preparation Cangzhu are used in China, Korea and Japan as Qi-booster. These preparations contain atractylenolides, a small group of sesquiterpenoids endowed with antioxidant and anti-inflammatory properties. Atractylenolides I, II and III also display significant anticancer properties, reviewed here. The capacity of AT-I/II/IIII to inhibit cell proliferation and to induce cancer cell death have been analyzed, together with their effects of angiogenesis, metastasis, cell differentiation and stemness. The immune-modulatory properties of ATs are discussed. AT-I has been tested clinically for the treatment of cancer-induced cachexia with encouraging results. ATs, alone or combined with cytotoxic drugs, could be useful to treat cancers or to reduce side effects of radio and chemotherapy. Several signaling pathways have been implicated in their multi-targeted mechanisms of action, in particular those involving the central regulators TLR4, NF kappa B and Nrf2. A drug-induced reduction of inflammatory cytokines production (TNF alpha, IL-6) also characterizes these molecules which are generally weakly cytotoxic and well tolerated in vivo. Inhibition of Janus kinases (notably JAK2 and JAK3 targeted by AT-I and AT-III, respectively) has been postulated. Information about their metabolism and toxicity are limited but the long-established traditional use of the Atractylodes and the diversity of anticancer effects reported with AT-I and AT-III should encourage further studies with these molecules and structurally related natural products.

Automated summary

The rhizome of Atractylodes macrocephala Koidz, a major constituent of Traditional Chinese Medicine Bai Zhu, contains atractylenolides with antioxidant and anti-inflammatory properties. These compounds show significant anticancer and immune-modulatory effects, inhibiting cell proliferation, inducing cancer cell death, and potentially reducing side effects of chemotherapy and radiotherapy. Possible mechanisms include inhibition of Janus kinases and involvement of key signaling pathways such as TLR4, NF kappa B and Nrf2. Further research on their metabolism, toxicity and potential in cancer treatment is warranted.