Halophytes comprise more than 350 annual and perennial species capable of tolerating the severe environmental condition of high salinity. In recent years, these plants have aroused interest as a valuable environmental resource for their ability to generate biomass in drought and salinity and a high resistance to conventional plant diseases. Moreover, halophytes contribute to carbon stabilization and play a role in soil phyto-desalinization and phytoremediation [1]. In addition to these benefits, halophytes have been attributed with health-promoting effects, including anti-inflammatory and antioxidant activities [2].

Salicornia ramosissima, also known as glasswort, is an annual halophyte of the S. europaea agg that can be found on the coastline of Europe, including Portugal and Spain, where its aerial parts are frequently consumed as a fresh vegetable [3]. More recently, the use of halophytes has been suggested as an alternative natural solution to reduce the sodium content of food products that are traditionally produced using salt [4]. S. ramosissima has a good nutritional profile, being a source of mineral and fiber [5], but also bioactive compounds. synthesized in response to abiotic stress due to high salinity and UV radiation, such as polyphenols, dietary consumption of which is associated with many health benefits.

Improving nutritional lifestyle is a major strategy in controlling modifiable risk factors related to cardiovascular and cerebrovascular diseases. Stroke, which is the most common neurovascular disease, represents the second cause of death and the third cause of disability worldwide according to the World Health Organization. Hemorrhagic stroke is caused by bleeding blood vessels and represents about 15% of all stroke cases. Ischemic stroke, which is the most common type, is caused by the occlusion of a blood vessel by a thrombus, resulting in the local lack of oxygen and nutrients leading to brain cell death at the infarcted area [6]. Given the high demand for oxygen and glucose of the tissue, the local disruption of blood flow to a brain area leads to cell death by necrosis within minutes (ischemic core). This event is followed by the disruption of normal cell function in the surrounding area (penumbra), triggered by energetic failure, inflammation, acidosis, excitotoxicity, release of Reactive Oxygen Species (ROS) and the impairment of the blood–brain barrier (BBB), among other mechanisms [7].

Reperfusion therapies using thrombolytics or mechanical thrombectomy are the current available treatments for ischemic stroke [8]. Although reperfusion is certainly the therapeutic objective, it can also induce additional injury by triggering inflammation and oxidative stress [9]. Two major categories of experimental models of brain ischemia are used in the search for new therapies for stroke in a variety of animal species including rats and mice, namely global and focal ischemia. The most common method used for focal ischemia is middle cerebral artery occlusion (MCAO), which can be permanent or transient, in order to allow reperfusion. In global ischemia, multiple cervical vessels are temporarily occluded [10].

It has been shown that a substantial proportion of strokes can be attributed to unhealthy lifestyle behaviors [11] and up to 80% of stroke recurrence might be prevented by the application of a multifactorial approach that includes dietary modification [12]. Recently, theour group reported that diet supplementation with S. ramosissima ethanolic extract with high content of polyphenols protected both flies and mice from the deleterious effects of ischemia [13]

2. Natural Bioactive Compounds Found in S. ramosissima

Saline stress response in Salicornia species comprises major events in plant tissues including osmotic, anatomical and physiological adaptations, as well as metabolic changes that involve the production of secondary metabolites [14]. On the basis of their structure and chemical nature, there are three main groups of secondary metabolites biosynthesized by plants: (i) terpenes, (ii) phenolics and (iii) sulfur and nitrogen-containing compounds (glucosinolates and alkaloids, respectively) [15]. Phenolics are a broad group of secondary metabolites that range from an aromatic ring (bearing one or more hydroxyl substituents) to more complex examples. Plant phenolics are biosynthesized through the shikimic acid and phenylpropanoid metabolism pathways ^[16][17][16,17]. The biosynthesis of phenolic compounds in plants begins with the conversion of glucose to glucose-6-phosphate to produce either phosphoenolpyruvate (PEP) by glycolysis or erythrose-4-phosphate by the pentose phosphate pathway (PPP). PEP and erythrose-4-phosphate are used together to produce phenylalanine and tyrosine by the shikimic acid pathway, which involves seven sequential enzymatic steps. Phenylalanine and tyrosine are then channeled into the phenylpropanoid pathway to generate several phenolic compounds by means of five rate-limiting enzymes ^[15][17][18][15,17,18]. Among the compounds of interest in Salicornia species are polyphenols, characterized by the presence of phenol rings in their structure, ranging from simple molecules to complex polymers. Polyphenol subgroups include phenolic acids, flavonoids, lignans and stilbenes ^[14][17][14,17]. The main polyphenols found in S. ramosissima are phenolic acids and flavonoids, as shown in Table 1. However, it has been reported that the polyphenol content varies in response to salinity levels and other stress factors ^[14][19][14,19]. These compounds have been of interest in recent decades due to their therapeutic effect in different conditions, including a protective role in ischemia, anti-thrombotic effects and other health-promoting neurovascular benefits.

Polyphenol	Subclass	Compound	Ref.
Flavonoid	Dihydrochalcone	Phloretin	[20]
		Phloridzin	[20]
	Flavanol	Catechin	[20]
		Epicatechin	[20]
		(Epi)gallocatechin	[13]
		Dihydroquercetin (Taxifolin)	[21]
	Flavanone	Naringin	[20]
		Naringenin	[20]
	Flavone	Apigenin	[20]
		Apigenin-6-arabinosyl-8-glucoside (isoschaftoside)	[21]
		Chrysin	[20]
		Luteolin glucosyllactate	[13]
	Flavonol	Isorhamnetin	[22]
		Isorhamnetin 3-glucoside	[22]
		Isorhamnetin-7-O-(6-O-malonyl)-glucoside	[23]
		Isorhamnetin glucopyranoside	[13]
		Kaempferol	[20]
		kaempferol derivative	[21]
		kaempferol-3-O-glucoside	[20]
		kaempferol-3-O-rutinoside	[20]
		Myricetin	[20]
		Quercetin	[20]
		Quercetin-3-O-galactoside	[20]
		Quercetin glucoside	[13]
		Quercetin 3-glucoside (Isoquercitrin)	[21][22][23]	[21,22,23]
		Quercetin-malonyglucoside	[13][21]	[13,21]
		Quercetin-methyl-ether derivative (isomer 1 and 2)	[21]
		Quercetin-rhamnosyl-hexoside	[13][21]	[13,21]
		Rutin (quercetin 3 -O rhamnosyl glucoside, quercetin rutinoside, vitamin p)	[20]
Phenolic acids	Hydroxybenzoic acids	Cannabidiolic acid	[13]
		Salicylic acid derivative	[21]
		Sitostanol	[24]
		Syringic acid	[20]
		Tiliroside	[20]
		Vanillic acid	[20]
		Ellagic acid	[20]
		Gallic acid	[20]
		Gallocatechin	[24]
		Protocatechuic acid	[20]
		Protocatechuic-arabinoside acid	[21]
	Hydroxycinnamic acids	Cinnamic acid	[25]
		P	-coumaric acid (4-hydroxycinnamic acid)	[13]]	[13	[20]	,20	[21][23	,21,23]
		Sinapic acid (3,5-Dimethoxy-4-hydroxycinnamic acid)	[20]
		Ethyl (E)-2-hydroxycinnamate	[24]
		P	-coumaric acid benzyl ester derivative	[21]
		Quinic acid	[13][21][23]	[13,21,23]
		P	-coumaroylquinic acid (isomer 1 and 2)	[21]
		Caffeic acid	[20][22]	[20,22]
		Hydrocaffeic acid	[22]
		Caffeic acid-glucuronide-glucoside (isomer 1)	[21]
		Caffeoylquinic acid	[22]
		Chlorogenic acid (3-O-caffeoylquinic acid)	[20][21][23]	[20,21,23]
		Neochlorogenic acid (5-O-caffeoylquinic acid)	[13][21]	[13,21]
		Dicaffeoylquinic acid (isomer 1, 2, 3 and 4)	[13][22]	[13,22]
		3,4-Di-O-caffeoylquinic acid	[20][22]	[20,22]
		3,5-Di-O-caffeoylquinic acid	[20]
		3,5-Dicaffeoylquinic acid	[21]
		4,5-Dicaffeoylquinic acid	[21]
		Hydrocaffeoylquinic acid	[13][21][22]	[13,21,22]
		Dihydrocaffeoyl quinic acid	[22]
		Caffeoyl-hydrocaffeoyl quinic acid	[21][22]	[21,22]
		Tungtungmadic acid (3-Caffeoyl-4-dihydrocaffeoyl quinic acid) (isomer 1 and 2)	[13]
		Ferulic acid	[13][21][23][25]	[13,21,23,25]
		Ferulic-glucoside acid	[21]
		Trans-ferulic acid	[20]
	Coumarin	Scopoletin	[13][24]	[13,24]