**4. Pharmacological activity**

Basu et al., Youdim et al., and Mazz were reported that the strawberry is having a special role in cardiovascular diseases, when this fruit included in the regular diet it will inhibit platelet aggregation and inflammation, improve endothelial function, plasma lipid profile, elevate low-density lipid profile which is oxidation resistance and also modulate the metabolism of eicosanoid [46, 48–50]. Most of the researchers evaluated that due to the presence of vitamin C and phenolic compounds in the strawberry having **antioxidant** capacity [51–54]. It has been concluded that

strawberry is 40 times more efficient than cereals, 10 times more efficient than vegetables, and 4 times more efficient than other fruits [55]. The polyphenols like anthocyanin, 2,5-dimethyl-4-hydroxy-3-[<sup>2</sup> H] furanone, and ellagic acid shown the antioxidant property (*in vitro* model) and have high bioavailability (*in vivo* model) [56, 57]. The specific phytoconstituents like carotenoids, phytosterols, vitamins (A, C, and folic acid), vitamin precursors like calcium and selenium, polyphenols, and triterpene esters are reported **chemoprotective** activity in carcinogenesis (multistage) [58, 59]. Depending on the strawberry species anthocyanin [60–64], ellagitannins, and proanthocyanidins having **anti-tumorigenic** properties against multiple human cancer cells of *in vitro* and *in vivo* animal models [65, 66]. Tamara et al., 2019 evaluated that the methanolic extract of strawberry significantly declines 3 T3-L1 adipocyte differentiation, CCAAT adipogenic transcription factors, C/REB-α enhancer-binding protein, peroxisome proliferation-activated receptor (PPAR-γ), resistin, angiotensinogen and it stimulates the AMP-activated protein kinase (AMPKα), Sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC 1α) suggested that mitochondrial biogenesis elevation. Their evidence concluded that the strawberry methanolic extract has a capability of **antiobesity** activity [67]. Mahendri et al., 2020 their team effort was reported that anthocyanin is one of the photo molecules present in the strawberry having an **antidiabetic** effect by declining blood sugar levels, improving endothelial dysfunction, and blood vessel inflammation [68, 69]. Susan (2010), Pinto (2008), and Apostolidis (2006) et al., evaluated that the strawberry is having the potency to treat

hypertension by inhibiting α-glucosidase, α-amylase, and angiotensin-converting enzyme activities which are linked to type-2 diabetes. They finally concluded that the strawberry is having **antihypertension** properties [70–72]. Gasapirrini et al., 2017 they screened and proposed that the strawberry is having an **anti-inflammatory** effect by activation of the Nrf2-AMPK pathway and NF-kB pathway which also elevates the antioxidant defense [73]. The list of pharmacological properties are incorporated in **Figure 1**.

Al-Sanea et al., 2021 they made tremendous work by selecting the combination of ginger and strawberry methanolic extract were used for silver nanoparticle synthesis (AgNPs) and evaluated by utilizing TEM analysis, Fourier-transform infrared, spectroscopy ultraviolet–visible spectroscopy, zeta potential, dynamic light scattering technique, and docking studies that the combination is having antiviral activity against SARS-CoV-2 by targeting proteins like Mpro, ADP ribose phosphatase, NSP14, NSP16, PLpro, AAK1 and Cathepsin L [74]. **Fisetin** is one of the phytomolecules found in strawberries and other fruits as well as having different biological activities such as antioxidant, anti-inflammatory, **anti-osteoporotic**, anticancer, **antimicrobial**, and antidiabetic activities [75]. Especially Kaempferol glycosides like kaempferitrin (kaempferol 3,7-dirhamnoside) is one of the biomolecules of flavonoids possessing different pharmacological activities such as anti-apoptotic, pro-apoptotic, **anthelmintic**, ant-convulsant, antidepressant, **immunostimulatory**, cardioprotective, and natriuretic [76]. Afrin. S et al., their immense work has proved that the combination of strawberry tree honey and 5-fluorouracil is effective in adenocarcinoma and **metastatic colon cancer**. The combined treatment declined cell viability, oxidative stress, elevated MAPK, ATF-6, XBP-1 markers, enhanced cell cycle arrest, apoptotic genes, and modulates regulatory genes in cell line studies [77]. Specifically, anthocyanin and ellagic acid phytomolecules have a **neuroprotective** property from oxidative damage [78, 79]. Alarcon et al., 2015 their team effort finally reported that the strawberry possesses **anti-platelet** activity by declining specific signaling molecules such as sP-selectin, sCD40L, RANTES, and IL-1b levels [80]. The natural therapy of strawberries gives relief to those who are suffering from **constipation** and **hemorrhoids** [81].

**Figure 1.** *Pharmacological properties of strawberry.*
