Salvigenin, a Trimethoxylated Flavone from Achillea Wilhelmsii C. Koch, Exerts Combined Lipid-Lowering and Mitochondrial Stimulatory Effects

Abstract

Phytochemical analysis of the Iranian plant Achillea wilhelmsii led to the isolation of 17 pure secondary metabolites belonging to the classes of sesquiterpenoids and phenolics. Two of these compounds, named wilhemsin (7) and wilhelmsolide (9), are new sesquiterpenoids, and the first shows undescribed structural features. Their structures were elucidated through extensive spectroscopic analysis, mainly based on 1D and 2D NMR, and chemical derivatization. Starting from plant traditional use and previous reports on the activity of the plant extracts, all the pure compounds were evaluated on endpoints related to the treatment of metabolic syndrome. The sesquiterpene hanphyllin (8) showed a selective cholesterol-lowering activity (−12.7% at 30 µM), santoflavone (13) stimulated glucose uptake via the GLUT transporter (+16.2% at 30 µM), while the trimethoxylated flavone salvigenin (14) showed a dual activity in decreasing lipid levels (−22.5% palmitic acid biosynthesis at 30 µM) and stimulating mitochondrial functionality (+15.4% at 30 µM). This study further confirms that, in addition to the antioxidants vitexin, isovitexin, and isoschaftoside, A. wilhelmsii extracts contain molecules that can act at different levels on the metabolic syndrome symptoms.

Investigation of Anti-Inflammatory Properties, Phytochemical Constituents, Antioxidant, and Antimicrobial Potentials of the Whole Plant Ethanolic Extract of Achillea santolinoides subsp. wilhelmsii (K. Koch) Greuter of Balochistan

“…The plant belongs to Asteraceae or Compositae family, and the genus Achillea comprises over 120 species worldwide [5]. The plant is widely distributed in Asia particularly in Pakistan, Iran, and India [6]. The word Achillea was derived from the Greek word Achilles, which means "hero," and was mostly used to cure various diseases during battles [7].…”

“…The plant is best known for its pleasant fragrant aroma and traditionally used for treating a variety of health problems by local community [8]. Achillea wilhelmsii contains various chemical constituents including alkamides, alkaloids, carvacrol, linalool, αand β-pinene, borneol, sesquiterpenoids (wilhemsin and wilhelmsolide), monoterpenoids, caryophyllene, rutin, thujene, 1,4-cineol, and camphor [6]. It has been shown that Achillea contains bitter aromatic substances having imperative effects on nervous system and neurological diseases such as epilepsy, neurasthenia, and seizures [9].…”

Towards Bioprospection of Commercial Materials of Mentha spicata L. Using a Combined Strategy of Metabolomics and Biological Activity Analyses

“…This is in agreement with the studies where salvigenin and esculetin present low antioxidant activity. Indeed, salvigening is reported with lipid-lowering and mitochondrial-stimulating activity, while esculentin shows anti-inflammatory, anti-apoptotic, anticancer, antidiabetic, and neuroprotective activities [ 37 , 38 ]. The antimicrobial causality analysis shows that the compounds with the most significant influence on the MRSA and E. faecalis inhibition are chlorogenic acid and esculentin, which are metabolites that are reported as compounds with an antibiotic capacity on gram-positive bacteria [ 38 , 39 ].…”

Protective Effects of Tiaoganquzhi Decoction in Treating inflammatory Injury of Nonalcoholic Fatty liver Disease by Promoting CGI-58 and Inhibiting Expression of NLRP3 Inflammasome

“…It has been reported that ferulic acid can ameliorate hepatic inflammation and modulate specific gut microbiota and genes involved in TG and TC metabolism ( Ma et al, 2019 ; Wu et al, 2021 ). Salvigenin improve the metabolic syndrome symptoms by decreasing lipid levels and stimulating mitochondrial functionality and it also help cells to survive by inhibiting apoptosis and enhancing autophagy ( Rafatian et al, 2012 ; Serino et al, 2021 ). Saikosaponin A, modulate glycerolipid metabolism role by regulating Lipe and Lipg and transcription factors peroxisome proliferator-activated receptor alpha (PPARa) ( Li et al, 2021 ).…”