Astragaloside IV derived from Astragalus membranaceus: A research review on the pharmacological effects

Decoctions prepared from the roots of Astragali Radix are known as "Huangqi" and are widely used in traditional Chinese medicine for treatment of viral and bacterial infections, inflammation, as well as cancer. Astragaloside IV (AS-IV), one of the major compounds from the aqueous extract of Astragalus membranaceus, is a cycloartane-type triterpene glycoside chemical. To date, many studies in cellular and animal models have demonstrated that AS-IV possesses potent protective effects in cardiovascular, lung, kidney and brain. Based on studies over the past several decades, this review systematically summarizes the pharmacological effects, pharmacokinetics and the toxicity of AS-IV. We analyze in detail the pharmacological effects of AS-IV on neuroprotection, liver protection, anti-cancer and anti-diabetes, attributable to its antioxidant, anti-inflammatory, anti-apoptotic properties, and the roles in enhancement of immunity, attenuation of the migration and invasion of cancer cells and improvement of chemosensitivity of chemotherapy drugs. In addition, the latest developments in the combination of AS-IV and other active ingredients of traditional Chinese medicine or chemical drugs are detailed. These pharmacological effects are associated with multiple signaling pathways, including the Raf-MEK-ERK pathway, EGFR-Nrf2 signaling pathway, Akt/PDE3B signaling pathway, AMPK signaling pathway, NF-κB signaling pathway, Nrf2 antioxidant signaling pathways, PI3K/Akt/mTOR signaling pathway, PKC-α-ERK1/2-NF-κB pathway, IL-11/STAT3 signaling pathway, Akt/GSK-3β/β-catenin pathway, JNK/c-Jun/AP-1 signaling pathway, PI3K/Akt/NF-κB pathway, miRNA-34a/LDHA pathway, Nox4/Smad2 pathway, JNK pathway and NF-kB/PPARγ pathway. This review will provide an overall understanding of the pharmacological functions of astragaloside IV on neuroprotection, liver protection, anti-cancer and anti-diabetes. In light of this, AS-IV will be a potent alternative therapeutic agent for treatment of the above mentioned diseases.