Phytochemicals from Achillea fragrantissima are Modulators of AβPP Metabolism

Abstract

Plant derivatives offer a novel and natural source of therapeutics. The desert plant Achillea fragrantissima (Forssk) Sch. Bip (Af) is characterized by protective antioxidative and anti-inflammatory properties. Here, we examined the effect of two Af-derived phytochemicals on learning and memory, amyloid-β protein precursor (AβPP) metabolism, and tau phosphorylation in the familial Alzheimer’s disease-linked APPswe/PS1∆E9 mouse model. We observed that mice that were injected with the phytochemicals showed a trend of improvement, albeit statistically insignificant, in the Novel Object Recognition task. However, we did not observe improvement in contextual fear conditioning, suggesting that the benefits of treatment may be either indirect or task-specific. In addition, we observed an increase in the full-length form of AβPP in the brains of mice treated with Af–derived phytochemicals. Interestingly, both in vivo and in vitro, there was no change in levels of soluble Aβ, oligomeric Aβ, or the carboxyl terminus fragments of AβPP (APP-CTFs), suggesting that the increase in full length AβPP does not exacerbate AβPP pathology, but may stabilize the full-length form of the molecule. Together, our data suggest that phytochemicals present in Af may have a modest positive impact on the progression of Alzheimer’s disease.

Antitumor activity of methoxylated flavonoids separated from Achillea fragrantissima extract in Ehrlich’s ascites carcinoma model in mice

“…Cirsiliol was previously isolated from A. fragrantissima and showed cytotoxic activity against HepG2 cell lines (6). In addition, isolated cirsiliol from A. fragrantissima (7,9). Isolation and identification of cirsimaritin and eupatilin 7-methyl ether from A. fragrantissima herb were also reported, previously (6).…”

“…Four methoxylated flavonoids were isolated from the extract, namely chrysosplenol D, cirsiliol, cirsimaritin, and eupatilin-7-methyl ether. The methoxylated flavonoids have been used as a dietary supplement in cancer prevention (7). In addition, the antiproliferative activities of these flavonoids have been reported and can be considered a promising target for new researches (6)(7)(8)(9)).…”

“…The methoxylated flavonoids have been used as a dietary supplement in cancer prevention (7). In addition, the antiproliferative activities of these flavonoids have been reported and can be considered a promising target for new researches (6)(7)(8)(9)). The present study described the antitumor activities of the extract and the flavonoid compounds and attempted to explain the mechanisms underlying these activities.…”

Functional profiling of Achillea fragrantissima (a perennial edible herb) against human cancer cells and potential nutraceutical impact in neutralizing cell proliferation by interfering with VEGF and NF-κB signaling pathways

“…The estimation was made for different kinds of molecules such as flavonoids, tannins, phenolics, saponins, and alkaloids, which are present in varying concentrations in the hydro-alcoholic extract, as shown in Figure 1. Specifically known phytochemicals (Table 1) present in this plant include sesquiterpene lactone, Achillolide A, 3,5,4'trihydroxy-6,7,3'-trimethoxyflavone, cirsiliol, cirsimaritin, and a number of hydrocarbon compounds which have been reported to possess pharmacological properties including anticancer effects (Barda et al, 2021;Bartolotti et al, 2018;Patocka and Navratilova, 2019). Studies have shown that various secondary metabolites of plant origin have the ability to inhibit the process of carcinogenesis in preclinical and clinical models (Ullah et al, 2014).…”

Achillea fragrantissima Essential Oil, Wild Grown in Saudi Arabia and Egypt: Detailed Comparative Chemical Profiling, and Evaluation of Allelopathic, Antioxidant, and Antibacterial Activities

“…A. fragrantissima is one of the common plants in different areas around the world and especially in the Arabian region, with several traditional uses as diuretic and for the treatment of stomach complaints, skin conditions, hepatic disease, inflammation, diabetes, dysmenorrhea, respiratory complaints, as well as for the treatment of eye infections and wound healing [7][8][9][10][11]. Additionally, the extracts of different parts of this plant are well known for having significant antioxidant, anti-tumor, antitrypanosomal, antimicrobial, analgesic, antidiabetic, neuroinflammatory and neuroprotective, and anti-inflammatory potentialities due to their chemical constituents [8,9].…”