Assessment of the biosafety profile of Galium verum in vitro on myoblasts and in ovo on chorioallantoic membrane

Table 1 Calculated irritation score for 200 μg/mL ethanolic extract of G. verum, H₂O (negative control), and 1% sodium dodecyl sulfate (positive control)

Sample	IS	Irritation category
H2O	0.070	Non-irritant
1% SDS 1%	18.501	Severe irritant
200 μg/mL Gallium verum	5.230	Irritant

IS: Irritation score; SDS: Sodium dodecyl sulfate.

Table 2 Effective natural sources in treating cardiac ischemia

Natural source	Active compounds	Effect on the ischemic myocardium	Ref.
Ginkgo biloba L.	Flavonoids, terpenoids, ginkgolic acids	Reduce angina and myocardial ischemia symptoms	[46,47]
Vitis vinifera L.	Resveratrol	Defense against ischemia-reperfusion injury	[31,32]
		↓ H3K27me3 levels, ameliorating hypertension status
		Promoting mitochondrial biogenesis
Gynostemma pentaphyllum Thunb.	Gypenoside A	↓ apoptosis and ↑ cell viability and proliferation on human cardiomyocytes	[38]
Citrus x aurantium L.	Hesperidin	Anti-apoptotic effects by ↑ Bcl-2 protein and ↓ Bax protein expression	[41,42]
		Induction in the expression of peroxisome proliferatoractivated receptorγ
		↓ JNK and p38-MAPK
Herba Siegesbeckiae	Kirenol	Protection against the aggravation of cardiac function in myocardial ischemia/reperfusion injury rats	[33]
		↓ inflammation and oxidative stress process
		Anti-apoptotic effect
		Blocking the activation of the NF-κB pathway reducing inflammation and oxidative stress
Momordica charantia L.	Terpenoids, tannins, saponins, flavonoids, and steroids	↓ Creatine kinase MB, heme oxygenase 1, tumor necrosis factor α, C-reactive protein, interleukin-6, and cardiac troponin I levels	[34,35]
		Restoring isoprenaline-induced abnormal electrocardiogram changes to normal levels
Morus alba L. Psidium guajava L., Psidium guajava L. Maclura pomifera Raf., Maclura tinctoria L., Malus pumila Borkh., Allium cepa L., Prunus amygdalus Batsch	Morin	↓ inflammation (TNF-α/IL-6/NFκB/IKKβ) and apoptosis (increased Bcl-2, decreased Bax/caspase-3 and TUNEL positivity) in the myocardium	[39,40]
Vitis vinifera L.; Allium cepa L.; Fragaria x ananassa Duchesne	Fisetin	↓ RAGE/NF-κB mediated oxidative stress, apoptosis, and inflammation	[43]
Lagerstroemia speciose L.	Corosolic acid	Protection of the heart against ischemia-reperfusion injury	[36]
		↓ oxidative stress and improving mitochondrial structure and function in cardiomyocytes
		↑ The expression of the mitophagy-related proteins prohibitin 2, PTEN-induced putative kinase protein-1, and parkin
		Protective effect on hypoxia and reoxygenation in cardiomyocytes
Salvia miltiorrhiza Bunge	Salvianolic acid	Improving ST segment changes
		↑ antioxidant, anti-inflammatory, and anticoagulant potential	[37]
Glycine max (L.)	Genistein	Regulation of P2X7/NF-κB pathway	[44]
Scutellaria baicalensis Georgi	Baicalin	↓ oxidative stress, inflammation, and apoptosis by suppressing TLR4/MyD88/MAPKS/NF-κB pathway	[45]
Olea europaea L.	Apigenin and vitexin	↓ LDL cholesterol, lipid peroxidation	[48,49]
		↑ Antioxidant enzyme activity
Melissa officinalis L.		↓ peroxidation of lipids such as malondialdehyde	[50]
		Blood pressure, cardiac troponin I, and infarct size
Allium sativum L.	Hydrogen sulfide, apigenin, and vitexin	↓ lipid peroxidation and superoxide and hydroxyl radicals	[51-53]
		↑ antioxidative enzymes levels
		↓ rate of cellular metabolism
Avena sativa L.	Vitamin C	↓ blood cholesterol and arterial blockage	[54]
		Regulation of c-JNK and p38-MAPK pathways

↑: Upregulation; ↓: Downregulation.