Hepatotoxicity in cattle associated with Salvia reflexa diterpenes, including 7-hydroxyrhyacophiline, a new seco-clerodane diterpene

Authors: Gardner, Dale; Panter, Kip; Stegelmeier, Bryan; Stonecipher, Clinton - Clint

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/2021
Publication Date: 1/21/2021
Citation: Gardner, D.R., Panter, K.E., Stegelmeier, B.L., Stonecipher, C.A. 2021. Hepatotoxicity in cattle associated with Salvia reflexa diterpenes, including 7-hydroxyrhyacophiline, a new seco-clerodane diterpene. Journal of Agricultural and Food Chemistry. 69(4):1251-1258. https://doi.org/10.1021/acs.jafc.0c06390.
DOI: https://doi.org/10.1021/acs.jafc.0c06390

Interpretive Summary: A case of weed contaminated alfalfa hay poisoned over 500 cattle and causing the death of 165 animals was investigated. The main cause of death was determined to be acute liver disease caused by unknown hepatotoxic compounds in the weedy hay. We report here the chemical investigation of the hay and the identification of the toxic compounds. The hepatoxic compounds were identified as salviarin, salvianduline D, rhyacophiline and 7-hydroxyrhyacophiline. The identified diterpenes are known to be found among different Salvia species which led to finding dried plant parts of Salvia reflexa within bales of weedy hay and subsequently a population of S. reflexa was found along the field edges and irrigation ditch banks of the alfalfa hay field. It was thus determined that S. reflexa was responsible for the poisoning in cattle fed the contaminated hay.

Technical Abstract: A case of baled alfalfa hay contaminated with multiple weeds induced hepatoxicity and death in cattle. The hepatoxic compounds were isolated by bioassay guided fractionation using a mouse model and identified as salviarin, salvianduline D, rhyacophiline and 7-hydroxyrhyacophiline. The structure of 7-hydroxyracophiline has not been previously reported. All compounds were found to induce severe acute hepatic necrosis within 24 to 48 hours after a single oral dosage (260 - 280 mg/kg). The identified diterpenes are known to be found among different Salvia species which led to finding dried plant parts of S. reflexa within bales of weedy hay and subsequently a population of S. reflexa was found along the field edges and irrigation ditch banks of the alfalfa hay field. It was thus determined that S. reflexa was responsible for the hepatotoxicity observed in cattle fed the contaminated hay.