Date Published: May 2, 2018
Author(s): Ammara Riaz, Azhar Rasul, Ghulam Hussain, Muhammad Kashif Zahoor, Farhat Jabeen, Zinayyera Subhani, Tahira Younis, Muhammad Ali, Iqra Sarfraz, Zeliha Selamoglu.
Natural products, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovery of drugs. This review article intends to emphasize on one of the naturally occurring flavonoids, astragalin (kaempferol 3-glucoside), which is a bioactive constituent of various traditional medicinal plants such as Cuscuta chinensis. This multifaceted compound is well known for its diversified pharmacological applications such as anti-inflammatory, antioxidant, neuroprotective, cardioprotective, antiobesity, antiosteoporotic, anticancer, antiulcer, and antidiabetic properties. It carries out the aforementioned activities by the regulation and modulation of various molecular targets such as transcription factors (NF-κB, TNF-α, and TGF-β1), enzymes (iNOS, COX-2, PGE2, MMP-1, MMP-3, MIP-1α, COX-2, PGE-2, HK2, AChe, SOD, DRP-1, DDH, PLCγ1, and GPX), kinases (JNK, MAPK, Akt, ERK, SAPK, IκBα, PI3K, and PKCβ2), cell adhesion proteins (E-cadherin, vimentin PAR-2, and NCam), apoptotic and antiapoptotic proteins (Beclin-1, Bcl-2, Bax, Bcl-xL, cytochrome c, LC3A/B, caspase-3, caspase-9, procaspase-3, procaspase-8, and IgE), and inflammatory cytokines (SOCS-3, SOCS-5, IL-1β, IL-4, IL-6, IL-8, IL-13, MCP-1, CXCL-1, CXCL-2, and IFN-γ). Although researchers have reported multiple pharmacological applications of astragalin in various diseased conditions, further experimental investigations are still mandatory to fully understand its mechanism of action. It is contemplated that astragalin could be subjected to structural optimization to ameliorate its chemical accessibility, to optimize its absorption profiles, and to synthesize its more effective analogues which will ultimately lead towards potent drug candidates.
Medicinal plants have been an infinite source of therapeutic agents since millions of years. Most of the discovered drugs either belong to natural products or derivatives of natural compounds [1, 2]. The actual fact is that nature is the creator of seemingly limitless series of molecular structures. These structures can serve as unlimited sources for the development of drugs, robust chemotypes, and pharmacophores which are able to be amplified into scaffolds of novel drugs for the cure of various ailments . Before the advent of the postgenomic era with high throughput screening, approximately 80% of drugs were either pure extracts of medicinal plants or the semisynthetic analogues of various compounds from natural sources . After the second world war, the pharmaceutical research expanded to massive screening of plant extracts in search of new drugs from natural resources . To date, about 61% of anticancer and 49% of anti-infective compounds have been discovered from natural products .
Astragalin, a naturally occurring flavonoid, has been identified in a variety of plants (Figure 1 and Table 1) such as Cuscuta chinensis Lam., a member of the Convolvulaceae family, which consists of about 60 genera and 1,650 species. The seeds of the genus Cuscuta are a rich source of astragalin and are utilized as a traditional folk medicine to cure osteoporosis in various Asian countries including Pakistan . C. chinensis has high contents of astragalin, that is, 29–34% of total phenolics as compared to other species . Cassia alata belongs to the family Fabaceae (the largest family among angiosperms) that comprises of ∼700 genera and 20,000 species. The leaves of C. alata are found to be effective against skin diseases including eczema and chronic skin impurities in tropical regions of the world (Malaysia, Brazil, and Indonesia) . Astragalin has also been isolated from the plants of Ebenaceae, Rosaceae, and Eucommiaceae families. The summary of plants containing astragalin, parts utilized, and biological features are enlisted in Table 1.
The biologically active and therapeutically effective compound “astragalin” has been known to possess broad spectrum of pharmacological features such as anticancer, anti-inflammatory, antioxidant, neuroprotective, antidiabetic, cardioprotective, antiulcer, and antifibrotic as shown in Figure 2. Various in vivo and in vitro investigations on astragalin have elucidated its medicinal characteristics and mechanism of actions.
ADMET profiles along with biological activity spectra were performed for astragalin based on in-silico tools. The results indicate that astragalin is a potential anticancer agent which is unlikely to present any acute hazard or toxicity. Furthermore, astragalin can be absorbed by human intestines, but it is incapable of penetration to Caco-2 cells. Astragalin has been validated as a novel substrate of p-glycoprotein which is crucial for the metabolism and clearance of the compounds and for the efflux of drugs .
Astragalin, a natural flavonoid, has been isolated from various traditional medicinal plants such as Cassia alata, Moringa oleifera, Nelumbo nucifera, Cuscuta spp., Radix astragali, Morus alba, and Eucommia ulmoides. Astragalin has been reported to modulate inflammatory responses by regulating the expression of NF-κB, iNOS, cytokines/chemokines (COX-2, TNF-α, IL-10, and IL-6), MAPK signaling pathways (PGE2, IgE, IL-4, IL-5, IL-13, IL-1β, and IL-6), and PAR2 signaling expression. It also has the capability to alleviate the production of ROS and inhibit the endotoxin-induced oxidative stress (Figure 3). Astragalin is also known to be an inhibitor of ERK-1/2 and Akt signaling; therefore, it is a significant compound against cancer proliferation. In this review paper, we have emphasized on various pharmacological properties of astragalin such as anti-inflammatory, antioxidant, neurological, cardioprotective, antidiabetic, and anticancer. Although several in vitro and in vivo investigations have demonstrated its diversified pharmacological applications, further experimentation along with medicinal chemistry approaches and preclinical trials is still obligatory to uncover the knowledge of its biological and pharmacological applications and their associated mechanisms of actions for the treatment and prevention of several diseases.