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Almutairi, F.M.;  Ullah, A.;  Althobaiti, Y.S.;  Irfan, H.M.;  Shareef, U.;  Usman, H.;  Ahmed, S. Promising Phytocompounds for Stroke. Encyclopedia. Available online: https://encyclopedia.pub/entry/31805 (accessed on 17 April 2024).
Almutairi FM,  Ullah A,  Althobaiti YS,  Irfan HM,  Shareef U,  Usman H, et al. Promising Phytocompounds for Stroke. Encyclopedia. Available at: https://encyclopedia.pub/entry/31805. Accessed April 17, 2024.
Almutairi, Farooq M., Aman Ullah, Yusuf S. Althobaiti, Hafiz Muhammad Irfan, Usman Shareef, Halima Usman, Sagheer Ahmed. "Promising Phytocompounds for Stroke" Encyclopedia, https://encyclopedia.pub/entry/31805 (accessed April 17, 2024).
Almutairi, F.M.,  Ullah, A.,  Althobaiti, Y.S.,  Irfan, H.M.,  Shareef, U.,  Usman, H., & Ahmed, S. (2022, October 28). Promising Phytocompounds for Stroke. In Encyclopedia. https://encyclopedia.pub/entry/31805
Almutairi, Farooq M., et al. "Promising Phytocompounds for Stroke." Encyclopedia. Web. 28 October, 2022.
Promising Phytocompounds for Stroke
Edit

Stroke is a serious condition that results from an occlusion of blood vessels that leads to brain damage. Globally, it is the second highest cause of death, and deaths from strokes are higher in older people than in the young. There is a higher rate of cases in urban areas compared to rural due to lifestyle, food, and pollution.

stroke phytocompounds occlusion of blood paralysis

1. Vitexin

Vitexin is a plant-derived phytochemical (Figure 1) present in many medicinal, and several other non-medicinal, plants, such as the passion flower, bamboo leaves, hawthorn, and chasteberry [1]. Chemically vitexin is a flavone C-glycoside (apigenin-8-C-β-D-glucopyranoside) and has been utilized in many studies to evaluate its potential in the treatment of stroke (Figure 1). These studies have shown that vitexin causes the inhibition of MCAO-induced brain infarction and apoptosis in animal models. Moreover, vitexin also causes a reduction in the levels of certain mediators, such as LDH, MDA, and NO, that are usually elevated due to increased levels of MCAO [2]. The enhanced inflammatory response in MCAO was also reduced when tested on rat models. The probable mechanism was by regulating the release of pro-inflammatory cytokines, such as TNF-α and IL-6, and anti-inflammatory cytokines, such as IL-10. According to the results, it is suggested that vitexin has to potential to suppress autophagy dysfunction to reduce MCAO-induced cerebral ischemic stroke through the TOR/U1k1 pathway [3].
Figure 1. Promising phytocompound’s structures for stroke.

2. Eriodictyol

Eriodictyol is a phytochemical (Figure 1) present in several fruits, vegetables, and certain Chinese herbs. It was first isolated from a Chinese herb called Dracocephalum rupestre. In a study, it was observed that the oral administration of eriodictyol in the doses of 1 mg/kg, 2 mg/kg, and 4 mg/kg has the potential to inhibit the effects of MPO expression and inflammatory cascade in a rat model of permanent ischemic stroke. It is suggested that eriodictyol treatment causes the down-regulation of the expression of certain inflammatory mediators, such as iNOS and TNF-α in ischemic cortex, which leads to a reduction in infarct size, improvement in motor function, and reduction in the memory deficit in rat models of permanent ischemic stroke [4]. Eriodictyol-7-O-glucoside (Figure 1) in 30mg/kg doses has also shown some neuroprotection against cerebral ischemic injury via activation of the antioxidant signalling nuclear factors, such as the erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) [5].

3. Carveol

Carveol is a naturally occurring phytochemical of monocyclic monoterpenoid nature abundantly present in nature in several plants, such as caraway seeds, essential oils of orange peel, dill, blackcurrant berries, and black tea [6][7]. In a study, it was observed that carveol has the potential to activate the endogenous master anti-oxidant Nrf2, which ultimately causes the regulation of the expression of downstream anti-oxidants. This eventually led to the reduction in MCAO-induced neuro-inflammation and neurodegeneration in rat models [8].

4. Ferulic Acid

Ferulic acid is a biologically active phytochemical (Figure 1) present in many medicinal plants, such as Ferula foetida (asafoetida) and LC. In a study, it was observed that ferulic acid has superoxide radical scavenging activity and the potential to restore vasodilation in spontaneously hypertensive rat models [9]. Ferulic acid treatment in 100 mg/kg doses at the very start of the MCAO-induced stroke model has shown a reduction in infarct size and improvement in neurological deficits. The probable mechanisms were related to the effective inhibition of ICAM-1 and NF-kB and by decreasing the infiltration of MPO immune reactive cells [10].

5. Rosamirinic Acid

Rosamirinic acid (RA) is a naturally occurring phenolic phytochemical (Figure 1) present in many herbs such as rosemary and has been isolated from the Chinese herb Salvia miltiorrhiza [11]. In a study, it was revealed that RA treatment in 50 mg/kg doses causes the inhibition of HMGB1 expression and nuclear factor-kB activation, which helps in the reduction in BBB permeability and infarct size, and in the improvement of neurological deficits in rat models of cerebral ischemia-reperfusion injury [12].

6. Paeoniflorin

Paeoniflorin is a naturally occurring phytochemical (Figure 1) derived from certain varieties of Paeonia species, such as Paeinia lactiflora Pall. In a study, it was observed that paeoniflorin possesses anti-inflammatory properties. It was revealed that an IV administration of paeoniflorin at the doses of 10mg/kg, 15mg/kg, and 20mg/kg doses, 10 min before or 30 min after the MCAO-induced cerebral ischemia causes a reduction in infarct size and neurological deficits through inhibition of PMN infiltration and by the down-regulation of inflammatory factors, such as TNF-α, IL-1β, and ICAM-1 [13].

7. Allicin

Allicin is a sulphur-containing phytochemical (Figure 1) present in garlic species, such as Allium sativum [14]. Allicin is known to possess anti-inflammatory, antifungal, antioxidant, and anti-tumor properties [15]. In a study, it was revealed that in 50 mg/kg doses, allicin causes a reduction in the TNF-α levels and MPO activity. By inhibiting these inflammatory mediators, Allicin causes a reduction in infarct size and decreases brain edema. The authors also observed an improved neurological score in the experimental rat models of MCAO ischemic stroke [16].

8. Curcumin

Curcumin is a naturally occurring polyphenolic phytochemical (Figure 1) present in large quantities in the curry spice turmeric (Curcuma longa). It has been used for the treatment of several ailments in ancient Chinese and Indian medicine. In several studies, it was revealed that curcumin shows its effects by targeting multiple molecular targets, such as transcription factors and growth factors, along with their receptors [17]. Curcumin also possesses anti-inflammatory, antioxidant, anti-tumor, and cardiovascular-protective activities [18]. In 150–200 mg/kg doses, curcumin also possesses neuroprotective properties, which are due to the inhibition of leukocyte infiltration, regulation of microglia/macrophage polarization, and a reduction in the production of several inflammatory factors. Curcumin also inhibits autophagy against cerebral ischemia-reperfusion injury [19][20]. The inhibition of signalling pathways, such as TLR2/4-NF-kB, causes a reduction in MPO activity in ischemic stroke models [21].

9. Ginkgolide K

Ginkgolide K (GK) is a naturally-occurring phytochemical (Figure 1) isolated from the leaves of various Ginkgo species, such as Ginkgo biloba [22]. Ginkgolide K has been utilized as a traditional medicine in Chinese medicine for the alleviation of symptoms related to cerebrovascular and cardiovascular disorders. In an experimental study, it was observed that ginkgolides are the natural antagonists of platelet-activating factor (PAF) receptors. It possesses neuroprotective properties due to its potential to reduce inflammation and oxidative stress after ischemic reperfusion injury. In recent years, Ginkgolide has caught the eye of many researchers worldwide owing to its potential in the treatment of stroke and cardioprotective properties against endoplasmic reticulum stress injury after an episode of ischemia [22]. It is suggested that GK possesses a dual role in neuronal protection after ischemic reperfusion injury through the inhibition of mitochondrial fission caused by the phosphorylation of Drp1 (Ser637) and reducing mPTP opening in a GSK-3β-dependent manner in neurons. The available data suggests that Drp1 and GSK-3β might be important factors in the opening of mPTP after cerebral ischemic reperfusion injury [23].

10. 6″-O-succinylapigenin

6″-O-succinylapigenin is a phytochemical (Figure 1) which is generally derived from apigenin and present in many different herbs. Zhang et al. observed that the administration of 6″-O-succinylapigenin in MCAO-induced stroke rats causes a reduction in infarct volume and also causes an improvement in many neurological deficits. Moreover, it also possesses anti-oxidant properties and when administered in rat models, it causes the increase in SOD and HO-1 levels and a reduction in MDA. It also possesses the ability to restore the levels of phosphorylated ERK/ERK [24].

11. Forsythiaside A

Forsythiaside A (FA) is a biologically-active phytochemical (Figure 1) present in large quantities in the fruits of Forsythia suspense [25]. In a study, it was found that FA possesses protective action in MCAO-induced rat models. FA possesses anti-oxidant properties by increasing the protein levels of Nrf2, NQO1, and GST, due to which, when administered in MCAO rats, it increased the survival rates by decreasing neurological deficits and apoptosis. FA has also been found to cause a reduction in serum MDA, an increase in SOD and GSH levels, and a reduction in endoplasmic reticulum stress [25].

12. Isoquercetin

Isoquercetin (Iso) is a phytochemical (Figure 1) present in various medicinal, as well as dietary plants, including several fruits and vegetables, and their derived drinks [26]. Dai et al. studied the protective mechanisms of Iso in ischemic reperfusion-injured rat models. Iso, when administered to MCAO-induced rats, causes a reduction in infarct size and cerebral edema. The results were more pronounced in rats that received the highest tested dose of Iso. Iso also improved the neurological score. In a study, it was also found that Iso possesses antioxidant properties and exerts its antioxidant action by causing a reduction in ROS and MDA levels and an increase in the levels of SOD and CAT in the hippocampi of MCAO-induced rat models. They also found that treatment with Iso also causes a reduction in apoptosis and increases the translocation of Nrf2 into the nucleus of the cell, thereby inhibiting the NOX4/ROS/NF-kB pathway. The in vitro analysis showed the same results when hippocampal neurons were exposed to OGD. However, it was observed that when the Nrf gene was knocked down, it suppressed the protective effects of Iso [27].

13. Trilobatin

Trilobatin (TLB) is a plant-derived phytochemical (Figure 1) and one of the main constituents of Lithocarpus polystachyus. In an experimental study, Gao et al. observed that it helps in improving neurological deficits, and brain edema and reducing infarct volume in MCAO-induced rat models. Moreover, they also estimated the time window for the administration of TLB after MCAO, which indicated that TLB in doses of 20mg/kg exerted a neuroprotective action after MCAO within the 4 hours. However, the protective effects were lessened when administered at 6 hours after MCAO. It was also found that TLB causes the restoration of long-term neurological functions. The neuroprotective effects of TLB were due to its ability to suppress the inflammatory cascade, which was evidently seen by the reduction in astrocyte and microglia activation, and decreased levels of pro-inflammatory markers. TLB also suppressed the levels of ROS and MDA and increased the activities of SOD and GPx. The antioxidant action of TLB was also associated with the upregulation of several nuclear factors, such as Nrf2, NQO1, and HO-1 expression, together with the suppression of Keap1. TLB also causes an elevation in the expression of Sirt3. In vitro replicative studies also showed the same results [28].

4.14. Genistein

Genistein (Gen) is a naturally-occurring isoflavone phytoestrogen (Figure 1) found in great proportion in soy foods. Several studies have shown that Gen has the potential to lessen the harm caused by both focal and global cerebral ischemia (GCI) in female mice with ovariectomy [29]. It is suggested that Gen treatment may reduce acute injury caused by cerebral ischemia in reproductively senescent mice through the inhibition of NLRP3 inflammasome present in microglia. This suggested that Gen may be a drug candidate for treatment of stroke in postmenopausal women [30].

15. Tocotrienol

Alpha-tocotrienol (Natural vitamin E) occurs in palm oil, wheat germ, barley, etc (Figure 1). It provides protection against ischemic stroke by induction of MRP1. The intracellular outflow of oxidised glutathione from brain cells is mostly mediated by MRP1. This is due to the potential for brain-cell death caused by an increase in intracellular oxidised glutathione. Tocotrienol can also promote neuroprotection by controlling the expression of microRNA in stroke-affected brain tissue. It has been demonstrated that vitamin E helps prevent ischemic stroke. However, it also raises the risk of subarachnoid haemorrhage [31][32][33].

References

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