Antioxidants are those chemical substances that can negate the harmful effects of free radicals and hence prevent the tissues from getting damaged. As such, they help safeguard against CVD (Michel et al., 2020). The generation of reactive oxidative species (ROS) can lead to oxidative stress and attack the vital biomolecules of the body, leading to damage to endothelial cells and vascular tissues. This can also lead to atherosclerosis and the conditions may become fatal over time (Taleb et al., 2018). It has been reported that natural antioxidants, especially from plant sources, have a tremendous potential for scavenging free radicals, chelating metal ions, enhancing the endogenous antioxidant system, and further preventing the formation of reactive species (Supplementary Table S3); hence, there are an intense and aggressive search plant-based antioxidants (Amic et al., 2003; Seyoum et al., 2006). Common bioactive drugs of Lamiaceae like oregano (Origanum vulgaris L.), rosemary (Rosemarinus officinalis L.), basil (Ocimum basilicum L.), thyme (Thymus vulgaris L.), and sage (Salvia officinalis L.) possess high antioxidant properties; they are reported to have free radical scavenging activity which increases upon heat exposure and drying (Hossain et al., 2010). Medicinal plants of Lamiaceae, Lycopus europaeus L., Melissa officinalis L., and Prunella vulgaris L. have shown significant anti-oxidative activities by free radical scavenger effect on DPPH (SC₅₀ values ranging from 16.7 ± 1.1 to 221.8 ± 49.0 µΜ for the three plants), which have been reported to be higher than that of rosmarinic acid (SC₅₀: 5.5 ± 0.2 µM) (Michel et al., 2020). Thymus sipyleus Boiss. subsp. sipyleus var. sipyleus, Teucrium chamaedrys L., Mentha longifolia (L.) Hudson subsp. longifolia, Salvia limbata C.A. Meyer, and Thymus fallax Fisch. and Mey, are very rich in phenols and flavonoids—these impart antioxidant properties to the extracts of the plants which are capable of regenerating antioxidant properties in the lipid bilayer of cells (Özgen et al., 2006). Firuzi et al. (2010) estimated the antioxidant activity of 24 species of Lamiaceae from Iran that included plants like Ballota aucheri Boiss., Eremostachys adenantha Jaub. & Spach Ill, Otostegia michauxii Briq., Phlomis elliptica Benth., Phlomis olivieri Benth., Phlomis persica Benth., Thymus daenensis Celak., and nine species of Salvia by DPPH and FRAP assay—of these, Salvia santolinifolia Boiss. has the highest antioxidant activity, comparable to the positive control, ascorbic acid (Firuzi et al., 2010; Michel et al., 2020). The essential oils were obtained from the aerial parts of Lavandula angustifolia Mill. and Lavandula stoechas L. also show high antioxidant activity (Ziaee et al., 2015). In addition, the ethanolic extract of the leaves of sage contains a high amount of phenolic acids, which exhibit high antioxidant activity as the phenol ring can easily give up H₂ atoms (Ramu et al., 2012).

An increase in blood cholesterol and triglycerides are another cause of CVD. It can lead to atherosclerosis—the condition in which fat droplets and lipids get deposited and hardened in the arteries obstructing the free flow of blood. This leads to various cardiac and coronary diseases like stroke and vascular diseases. The ability of substances to break down these hardened fat depositions is called the antihyperlipidemic or hypolipidemic effect, which can lower the level of triglycerides like low-density lipoprotein (LDL) and cholesterol and help to increase the “good” high-density lipoprotein (HDL) (Akinpelu et al., 2016). Thus, they can alleviate the risk of CVD greatly. The extracts obtained from the different plant organs of Lamiaceae are very rich in polyphenols and exhibit an antihyperlipidemic effect. The dried hydroalcoholic extract Dracocephalum kotschyi Boiss (dosage 40 mg kg⁻¹ body weight) has been reported as the best dose for hyperlipidemia in rats and can significantly reduce the risk of atherosclerosis (Heydari et al., 2019). The ethanolic and ether extracts of Leucas aspera, which are used in folklore to treat various ailments, are rich in secondary metabolites. The steroidal phytochemicals tend to replace cholesterol in triglyceride formation that further leading to a hypolipidemic effect; the extract was effective in a dose-dependent manner in rat modes with induced hyperlipidemia (dexamethasone treatment) (Vijay Kumar and Devanna, 2016). Indian tulsi (Ocimum tenuiflorum L.) is traditionally used as an anti-tussive agent. The alcoholic extract of this plant has a no. of phenolic compounds—each of which has anti-hyperlipidemic activity. In addition, the extract (125–500 mg kg⁻¹ body weight) can lower the level of LDL and increase HDL up to the story of a healthy rat (Parasuraman et al., 2015). Aqueous extracts of Thymus saturejoides Coss. (0.2 g per 100 g of extract) can significantly lower blood plasma cholesterol and triglyceride levels—this decrease is associated with the reduction of LDL levels. Similarly, the aqueous extract of Teucrium polium L. (50–150 mg kg⁻¹ of extract) can decrease levels of cholesterol and triglycerides in the blood of hyperlipidemic rats in a dose-dependent manner (Khouya et al., 2015).

Blood clotting involves a complex series of events—the breakdown to protein activates the process of thrombin formation that further converts fibrinogen to fibrin. Factor VIII with platelets triggers this set of circumstances and aid in the process of blood clotting or blood coagulation. The formation of a thrombus or clot in the arteries and tissues is prevented by anticoagulants (Schaeffer and Zimlich, 2019). Few plants of Lamiaceae have been reported to possess anticoagulation potential. Ali et al. (2014) revealed thrombolytic activity of methanol extract and solvent fractions (petroleum ether, chloroform, carbon tetrachloride) and aqueous fractions of the leaves of Clerodendrum infortunatum L. by clot lysis assay; the carbon tetrachloride and chloroform fractions displayed the highest and least percentage of clot lysis. The different bits of the root extract of this plant also showed thrombolytic activity (Ali et al., 2014; Prashith Kekuda et al., 2019). The leaf extracts of Salvia officinalis L., Thymus vulgaris L. and Rosmarinus officinalis L. (200–1,000 μg ml⁻¹) exhibit thrombolytic activity in a dose-dependent manner; their thrombolytic potential can be arranged in the order Salvia officinalis L. > Thymus vulgaris L. > Rosmarinus officinalis L. (Mutalib, 2015). In addition, Salvia miltiorrhiza (Bunge) also exhibited mild inhibition of platelet aggregation in vivo in rats. Another member of Lamiaceae, Leonotis leonurus (L.) R. showed anticoagulation potential both in vitro and in vivo. The plant extract lowered or prevented the expression of proteins responsible for platelet aggregation and blood clotting. At a concentration of 50–100 μg ml⁻¹, platelet adhesion was reduced in a dose-dependent manner, and preventing activation of thrombin and fibrinogen (Mnonopi et al., 2011).

Excessive contraction of blood vessels for a prolonged duration causes an increase in blood pressure, leading to hypertension. Vasorelaxants are drugs that can cause dilation of blood vessels that ensure the flow of blood through the vessels at ease—most of these cause relaxation of vascular smooth muscles—the most common method of treatment used for hypertension (Herradón et al., 2007). It has been reported that plant-based compounds like chalcones inhibit angiotensin-converting exam (ACE) through nitric oxide (NO)- and estrogen receptor α (ERα)-dependent pathways to bring about vasorelaxation and lower the risk of CVDs (Legeay et al., 2020). Agastache mexicana (Kunth.) Lint. and Epling, is a medicinal plant from the Lamiaceae family used for the treatment of anxiety. The antihypertensive activity of the plant extract was determined in the male rat - the extract exhibited relaxant activity and exhibited vasodilation effect through several receptors, such as the augment of free cytosolic Ca²⁺ levels; it further inhibited vasoconstriction and showed a diuretic effect, preventing hypertension (Hernandez-Abreu et al., 2013; Flores-flores et al., 2016). Senejoux et al. (2010) reported the vasodilation activity of Ziziphora clinopodioides Lam., a plant that finds its use in Chinese folk medicine for the treatment of hypertension. The decoctions of the whole plant of Z. clinopodioides decreased the influx of Ca²⁺ ions in KCl mediated contractions of vascular smooth muscles. Further, the vasorelaxation of this extract did not involve endothelium-derived relaxing factors like NO and prostacyclin (Senejoux et al., 2010). The sections of Clinopodium vulgare L., another member of the mint family, have vasodilation potential in rats both in vitro and in vivo. At a concentration of 1–30 mg kg⁻¹, the vasorelaxation in rat aorta was endothelium mediated, i.e. it involves muscular NO channels, K⁺ channels, together with the closure of Ca²⁺ ion channels, and occurred in a dose-dependent manner (Khan et al., 2018). The extract of Orthosiphon aristatus (Blume) Miq. Possesses vasorelaxation or vasodilation activity, which exhibited a relaxation on KCl-induced aortic rings of the endothelium and phenylephrine-induced aortic ring that may or may not have endothelium in rats; pathways that are involved in this vasorelaxant activity are NO/sGC/cGMP pathways (Yam et al., 2016, 2018). Other members of Lamiaceae that are engaged in vasorelaxation and vasodilation are Melissa officinalis L., Orthosiphon aristatus (Blume) Miq. (syn. Orthosiphon stamineus Benth.), Phlomoides bracteosa (Royle ex Benth.) Kamelin and Makhm., Plectranthus hadiensis (Forssk.) Schweinf. ex Sprenger (syn. Coleus forskohlii Willd.), Pogostemon elsholtzioides Benth, Satureja cuneifolia Ten. (syn. Satureja obovata Lag.), Sideritis raeseri Boiss. and Heldr (Michel et al., 2020).

Drugs that aid in diuresis can increase the urinary volume; this can lower the risk of heart disorders and ease out conditions like heart failure, pulmonary oedema, and stroke. Many drugs are available that can be used alone or in combination for diuresis, but they have a myriad of adverse effects with them. Research on plants and plant-based bioactive compounds suggests that plant species exhibit diuretic activity with negligible side effects; some plants of the Lamiaceae family have been reported for the same (Gupta and Neyses, 2005; Morganti, 2005; Michel et al., 2020). The different solvent extracts (aqueous, alcoholic and ethyl acetate) of the leaf of Plectranthus amboinicus (Lour) Spreng increases urine volume and decreases serum Na level of albino rats in comparison to the available drug but had no effect on the serum K level; the ethyl acetate fraction was more potent as a diuretic group with better electrolyte balance than the other solvent fractions (El-Hawary et al., 2012). The aqueous and ethanol extracts of Coleus amboinicus, Lour. Has also shown significant diuretic activity (Venkateshappa and Sreenath, 2013). Ajuga integrifolia Buch. -Ham. ex D. Don) is a perennial herbaceous plant of Lamiaceae that has significant diuretic activity; its aqueous and 80% methanolic extract showed an increase in urine volume and the diuretic effect, together with electrolyte excretion effect, was comparable to that produced by diuretic drug furosemide (Hailu and Engidawork, 2014). Clerodendrum myricoides Hoscht. has been used as a traditional medicine for curing various ailments like urine retention and oedema. This plant’s hydromethanolic leaf and root extracts and its fractions (ethyl acetate, chloroform, and alcohol) showed diuretic activity in rats in vivo—the hydromethanolic extract showed higher diuresis than furosemide (100 mg kg⁻¹). It is reported that this extract had higher solubility for pharmacologically active ingredients like flavonoids, tannins, terpenes, phenols, saponins and others, and they also act synergistically; moreover, this extract has very minimal cell cytotoxicity (Welu et al., 2020). Other plants from Lamiaceae that show diuretic activity are Anisomeles indica L., Teucrium polium L., and Ajuga integrifolia Buch. -Ham. ex D. Don (Malki and Yahia, 2014).

Plants of Lamiaceae possess promising benefits in reducing the risk of CVDs through the suppression of inflammation (Tzima et al., 2018). The methanolic extract of Satureja hortensis L. plant is well known for CVDs treatment and other related complications by inhibiting the secretion, aggregation and adhesion of the blood platelet and the anticoagulant activity blood (Hamidpour et al., 2014). The leaf extract of Ocimum basilicum L. showed an anticoagulant effect, as reported by Pour et al. (2016) (Pour et al., 2016). The Lavandula aguistifolia Mill. contain bioactive compounds such as flavonoids, tannins, triterpenoids, coumarins, cineole, limonene, and camphor showed substantial antioxidant properties with reduced cardiac tissue damage and strengthened myocardial membrane (Koshma et al., 2018). The plant extract of Leonotis leonurus (L.) R.Br. contains a primary compound named Marrubiin (labdane diterpenoid) exhibiting antiplatelet, anticoagulant, and anti-inflammatory properties (Mnonopi et al., 2011). The Leonurus turkestanicus V.I.Krecz. & Kuprian. as reported by (Mamadalieva et al., 2017), shown to be effective against cardiovascular, stomach, and other related diseases. As shown by histopathological analysis, Stachys schimperi Vatke possesses cardioprotective effects on DOX-induced cardiotoxicity in rats. Rosmarinic acid found in basil leaves (Ocimum basilicum L.) exhibited cardioprotective effects in rats with isoproterenol-induced myocardial infarction (Koshma et al., 2018). One of the major components found in most species of the Lamiaceae family, Thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) showed healing effects against apoptosis, coronary artery diseases, diabetes, urinary system failures, hypertension, inflammation, and oxidative stress which is related to its antioxidant and anti-inflammatory activity (Farkhondeh et al., 2017). Components such as methylripariochromene A, orthochromene A, neoorthosiphol A and B and tetramethylscutell isolated from the leaves of Orthosiphon species of Lamiaceae family have been studied and showed decreased systolic blood pressure (Singh et al., 2015). Essential oil of Lavandula angustifolia Mill. has been shown to protect isoproterenol-induced myocardial infarction in a study using rat antioxidant activity (Ziaee et al., 2015) (Table 3).

Incorporating bioactive drugs from the Lamiaceae family (sage, mint, rosemary, oregano, thyme) into the innovative functional foods on aroma compound formation and sensory properties oat-buckwheat products. Herbs of Lamiaceae contain a unique, complex mixture of bioactive compounds. They include secondary metabolites such as phenolic compounds, tannins, quinines, lignans, terpenoids, and flavonoids and they are also rich in essential oils and can enhance the taste and aroma of the final product (Vaishali Rai et al., 2013; Carović-Stanko et al., 2016; El-Sayed and Youssef, 2019). Most herbs and spices have relatively high micronutrients (minerals and vitamins), macronutrients (such as protein, fat, and carbohydrate) and fewer anti-nutritional properties. The total antioxidant potential of plant materials such as culinary herbs, spices, vegetables, as well as fruits and oilseed products are related to ascorbic acid (vitamin C), alpha-tocopherol (Vitamin E), beta-carotene (Vitamin A precursor), numerous flavonoids, and other phenolic compounds (Rather et al., 2016). Basil (Ocimum basilicum L.) is one of the most popular cultivated plants. It is a good source of natural antioxidants and contains significant amounts of essential phytochemicals. The inclusion of basil in the development of fresh cheese made with organic buffalo milk did not modify the fat, protein, moisture, and mineral content. In contrast, the total polyphenol content and antioxidant activity of cheeses increased. It also changed the hardened and chewiness but not influenced springiness and cohesiveness. Thus, the basil improves the functional and modified technological characteristics of fresh cheeses and presents good acceptability (Ribas et al., 2019). Food can be functional by increasing concentration, adding or improving the bioavailability of bioactive ingredients, such as probiotics, fibres, phytochemicals, vitamins, minerals, bioactive drugs, omega-3s, peptides-proteins (Roberfroid, 2002; Arvanitoyannis and Van Houwelingen-Koukaliaroglou, 2005). Basil (Ocimum basilicum L.) is rich in polyphenols, antioxidant, antimicrobial and antifungal properties (Carocho et al., 2016). The basil branches mainly contain fibers, essential oils and minerals, such as nitrogen, calcium, potassium and magnesium. Basil leaves have significant amounts of carotene, vitamin B (1, 2, 3), vitamin C, minerals (calcium, phosphorus and iron), polyphenols and essential oils (Dumbrava et al., 2012). Thus, it can be added to foods as a functional ingredient, such as dairy products. Phenolic compounds, secondary outcomes of plant metabolism, have been suggested as bioactive compounds due to their antioxidant capacity and beneficial effects on human health (Han et al., 2011). Additions of seasoning plants, rich in phenolic compounds, in cheeses have already been reported (Asensio et al., 2015).

Some of the bioactive compounds from the Lamiaceae plant family with cardio-protective and therapeutic properties include leonurine, rosmarinic acid, quercetin, apigenin, carvacrol, thymoquinone, baicalein, and many others (Table 3). The cardioprotective effects exhibited by these compounds are through multiple regulations, including growth factors, enzymes, kinases, apoptotic, transcription factors, and other molecules.

Apigenin has shown similar mechanisms in cardio-protection by inhibiting the phosphorylation of p38 MAPKS during myocardial I/R and reducing the activity of caspase-3 activity and Bax protein expression while the expression of Bcl-2 protein is increased (Hu et al., 2015; Chen Y. et al., 2017). Leonurine, a natural active compound of Leonurus cardiaca L. acts as an adjuvant cardioprotective agent and has anti-oxidative and anti-apoptotic properties (Liu et al., 2009, 2010) and also increases the hypoxia-inducible factor-1α (HIF-1α) in H9c2 cardiac myocytes expression and Akt phosphorylation (Liu et al., 2010) leading to suppression of cardiac cell death. Moreover, leonurine exerts potent cardioprotective effects by either increasing the level of p-PIK, p-AAKT, p-GSK3ß and Bcl-2, or decreasing the levels of caspase 3, cleaved-caspase3 and Bax (Xu et al., 2018). Rosmarinic acid displays effective cardioprotective effects by increasing the enzymes involved in antioxidant activity and regulating the sarcoplasmic reticulum Ca²⁺ homeostasis gene expression (Javidanpour et al., 2017). It also protects against cardiac fibrosis by inhibiting phosphorylation, activating the AMPKα, and nuclear translocation of Smad3 and attenuating cardiac fibrosis by inducing peroxisome proliferator-activated receptors (PPAR-γ) (Lu et al., 2018). Quercetin, found in many plants of Lamiaceae family, has potent cardioprotective effects by inhibiting the secretion of adenosine nucleotide from activated platelets and decreasing the neutrophil function (Kaneider et al., 2004) and reducing the plasma creatine kinase (CK), cardiac TBARS and NO(x) contents (Ahmed et al., 2009; Chiş et al., 2018). Another bioactive compound, viz., Carvacrol, possess cardioprotective activities by suppressing the myocardial ischemic damage and myocardial enzymes, including cardiac troponin T (cTnT), creatine kinase (CK) and lactate dehydrogenase (LDH). It elevates the activities of the antioxidant enzymes superoxide dismutase (SOD), non-enzymatic scavenger glutathione (GSH), and glutathione peroxidase (GSH-PX). It has been shown to inhibit the caspase-3 activation and Bax protein expressions but upregulated Bcl-2 protein expression while reducing the activity of malondialdehyde (Yu et al., 2013). The cardioprotective effects of carvacrol are through the two signalling pathways, viz., MAPK/ERK and Akt/eNOS (Chen Y. et al., 2017). Thymoquinone, one of the active constituents of Thymus plant species, improves cardiac and reduces infarct size and mediate by a decrease in cardiac lactate dehydrogenase and creatine kinase levels and suppressed non-oxidative stress and apoptosis (Xiao et al., 2018). The cardioprotective effect of thymoquinone is by the up-regulating of SIRT1 expression and inhibition of p53 acetylation (Lu et al., 2018). Baicalein, an active component found in Scutellaria baicalensis Georgi and Scutellaria lateriflora L. and other Lamiaceae plants, exhibits cardioprotective effects besides anti-inflammatory and antioxidant effects. The activation of MAPK and NF-κB pathways in rats is inhibited, decreasing MDA level and increasing the SOD and GSH-Px activity (Kumar et al., 2016; Shi et al., 2018). The compound baicalein, through the Nrf2/Keap1 pathway, protects cardiomyocytes against oxidative stress-induced cells (Cui et al., 2015). There are several other bioactive compounds from plants of Lamiaceae that have similar cardioprotective properties. Polyphenols display antioxidant effects and vasodilatory properties (Portincasa and Calamita, 2019) that reduce the cardiovascular impact. The intake of food rich in flavonoids, and anthocyanidins reduces the death rate due to cardiovascular diseases (Portincasa and Calamita, 2019). With advanced awareness on the benefits of nutraceuticals and plant-derived bioactive molecules for reducing the risk and incidence of CVDs, the demand for herbal formulations rich in antioxidants is increasing (Pandey et al., 2010) for the substitution of synthetic medicines for treating hypertension, hypercholesterolemia and cardiovascular disease. The stability and shelf-life of these bioactive compounds during designing for the prevention of CVDs and tailor-made foods is essential. With the emerging technologies in the last decade, such as high-pressure homogenization, pulsed electric fields, and other non-thermal technologies, gas-plasma were recommended to overcome the nutritional content loss due to the use of severe thermal treatments (Bekut et al., 2018; Do et al., 2018; Patrignani et al., 2021).

The aromatic Lamiaceae plants rich in phytochemicals have high antioxidant activity. The introduction of these phytochemicals into the traditional and modern food recipes has improved the nutritional quality of the foods (Figure 5). Lamiaceae family attains a significantly higher figure for cultural importance. This fact remarks the high significance of the vegetable and herbal tea category in most survey areas (Ali-shtayeh et al., 2008). Lamiaceae are often used in local cuisines to increase the digestibility of cooked food. This confirms that the uses of Lamiaceae plants in food can be relevant to the development of functional foods, pharmafoods or nutraceuticals as they are aromatic and contain many essential oils (da Silva et al., 2021). Akshomiya people, during the celebration of the harvest festival—Bihu, collect 101 plant species and prepare vegetable recipes in the evening containing four Lamiaceae species amongst other plants on the first day of the Bohag Bihu, also called Goru (cow) Bihu (Gogoi and Zaman, 2013). They believe that this particular recipe has some medicinal values, which is good for health for the next year too. Barros et al. (2011) have reported that several traditional recipes are flavoured by seasoning and to preserve food with the dried leaves and inflorescence of the different species of Lamiaceae plants. These plants are used in conventional delectable soups and summer salads. At the last minute, the fresh leaves of ground ivy are added in different types of soups, viz., soup made of potato, onion and chopped kale, bean soup, and chickpea-based soups. They are also used in stewed beans prepared with vegetables and sausages (Barros et al., 2011). It was reported that the phytochemicals in the refined flour are much lower since the bran and embryo fractions rich in those compounds are removed during the milling process as compared to the whole wheat grains used for the production of the traditional bread (Skendi et al., 2020b). So, the introduction of phytochemicals from the Lamiaceae plants will increase the nutritional quality of the final bread with many health benefits of daily consumption.

Enrichment of bread recipes with essential oils and dry form could inhibit the mycelia growth of Penicillium and Aspergillus fungi at a concentration range where the bread are considered acceptable based on sensory tests. Moreover, adding aromatic plants in the dry form in the bread recipe is more effective against both fungi studied than essential oils (Skendi et al., 2020a). Extensive studies have been carried out in the Lamiaceae family concerning the essential oils and their use as food preservatives (Debonne et al., 2018b; Císarová et al., 2018) and among them, oregano and thyme are of major importance due to their antimicrobial and antifungal activities (Debonne et al., 2018a; Císarová et al., 2018). Essential oils contain a variety of volatile molecules such as terpenes and terpenoids, phenol-derived aromatic components, and aliphatic compounds (Bakkali et al., 2008; Muslim and Hussin, 2020).