In Vivo Hepatoprotective and Nephroprotective Activity of Acylated Iridoid Glycosides from Scrophularia hepericifolia

SIMPLE SUMMARY: Chronic liver disease is a major life-threating problem worldwide. Deaths due to liver disease constituted 2.4% of total deaths globally in 2017. Yet most of the available drugs for improving liver conditions are of natural origin. More research is necessary to discover agents that are more effective. Previously, the extract of Scrophularia hypericifolia showed promising protection of liver and kidney tissues against induced toxicity in experimental animals. The current phytochemical study aimed to identify the active molecules in the extract. Nine iridoid glycoside derivatives were identified from the plant extract, including four new compounds after extensive chromatographic purification. The structures were identified by applying various spectroscopic methods. Biological evaluation for protective effect on liver and kidney tissues was conducted on compounds isolated with a high enough yield. Serum and tissue parameters as well as histopathological studies were conducted for efficacy evaluation. Two of the new compounds showed the best protection of liver and kidney tissues as indicated by the studied parameters. These findings indicated that natural products could provide solutions to health problems. The role of nutraceuticals in managing liver problems is a promising field for further studies. ABSTRACT: Phytochemical investigation of the chloroform fraction obtained from Scrophularia hypericifolia aerial parts led to the isolation of nine acylated iridoid glycosides. The new compounds were identified as 6-O-α-L(2″-acetyl, 3″,4″-di-O-trans-cinnamoyl) rhamnopyranosyl-6′-acetyl catalpol (6′-acetyl hypericifolin A) (1), 6-O-α-L(2″, 4″-diacetyl, 3″-O-trans-cinnamoyl) rhamnopyranosyl-6′-acetyl catalpol (6′-acetyl hypericifolin B) (2), 6-O-α-L(2″-acetyl, 3″,4″-di-O-trans-cinnamoyl) rhamnopyranosyl catalpol (hypericifolin A) (3) and 6-O-α-L(2″, 4″-diacetyl, 3″-O-trans-cinnamoyl) rhamnopyranosyl catalpol (hypericifolin B) (4). Previously reported compounds were identified as laterioside (5), 8-O-acetylharpagide (6), 6-O-α-L(4′-O-trans-cinnamoyl) rhamnopyranosyl catalpol (7), lagotisoside D (8) and harpagoside (9). Identification achieved via analyses of physical and spectral data including 1D, 2D NMR and High Resolution Electrospray Ionization Mass spectroscopy (HRESIMS). Compounds 2–4 and 6 were subjected to biological evaluation against paracetamol-induced toxicity. The biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) as well as total bilirubin were used to access the liver condition. Measurement of serum levels of urea, creatinine, sodium and potassium cations were indicators for kidney condition. Liver and kidney samples were subjected to histopathological study. The best protection was found in the group treated with 3 followed by 4 and 6, while 2 was almost inactive.