Oridonin derivative ameliorates experimental colitis by inhibiting activated T‐cells and translocation of nuclear factor‐kappa B

Abstract

HAO472 has positive effects on TNBS-induced colitis by modulating the subsets and functions of lymphocytes, suppressing inflammation and inhibiting the nuclear translocation of NF-κB p65 subunits.

Therapeutic Potential of Oridonin and Its Analogs: From Anticancer and Antiinflammation to Neuroprotection

“…HAO472 ( Figure 2 ) was designed with an alanine ester trifluoroacetate at the C-14 position to improve its aqueous solubility (i.e., 165 mg/mL). HAO472 was said to maintain the anticancer activities of oridonin (data not disclosed), while also being less likely to cause vascular injury [ 32 , 52 ]. Thus, in China, HAO472 has been advanced into Phase I human clinical trials for the treatment of acute myelogenous leukemia (80–320 mg/d, iv, CTR20150246).…”

“…Oridonin was reported to suppress the expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) by inhibiting NF-κB DNA binding activity in HepG2, RAW264.7, and Jurkat cells [ 61 , 62 ]. Several groups have shown that oridonin and its water-soluble derivative (HAO472, Figure 1 ) might ameliorate TNBS-induced colitis by decreasing Th1/Th17 via inhibiting NF-κB signaling, subsequently reducing TNF-α, TNF-γ, IL-17A, iNOS/COX-2, and lymphocyte proliferation [ 52 , 63 ].…”

Discovery and development of natural product oridonin-inspired anticancer agents

“…HAO472 was claimed to retain the anticancer activities of oridonin (data not disclosed) with less toxicity (no-observed-adverse-effect level, NOAEL = 40 mg/kg) and markedly improved drug-like properties [14]. Moreover, HAO472 was found to inhibit the proliferation and activation of T cells by down-regulating the NF-κB signaling pathway in the treatment of inflammatory bowel disease, which is an established colorectal cancer risk factor [64]. HAO472 has been advanced into Phase I human clinical trials in China for the treatment of acute myelogenous leukemia (80–320 mg/d, iv, CTR20150246).…”

Neuroprotective Effect of Oridonin on Traumatic Brain Injury via Inhibiting NLRP3 Inflammasome in Experimental Mice

“…In this study, it has been proved that Ori forms a covalent bond with cysteine 279 of NLRP3 in NACHT domain to block the interaction between NLRP3 and NEK7, thereby inhibiting NLRP3 inflammasome assembly and activation. Ori has also been reported to attenuate inflammation in various diseases such as rheumatoid arthritis, colitis, and AD (Wang et al, 2014;Liu et al, 2016;Shang et al, 2016). Based on these, the purpose of the current study was to investigate whether Ori could alleviate SBI after TBI via inhibiting the activation of NLRP3 inflammasome.…”