Virtual screening of functional foods and dissecting their roles in modulating gene functions to support post COVID‐19 complications – Afroz – – Journal of Food Biochemistry

2.1 Black cumin (Nigella sativa)

Black cumin (Nigella sativa), belonging to the household Ranunculaceae (Iqbal et al., 2017), has been very generally utilized in India and the Center Japanese inhabitants as a spice, preservative for meals and medication since way back. Its seeds are wealthy in oil, proteins, minerals, and carbohydrates (Iqbal et al., 2017). The oil accommodates unsaturated fatty acids, terpenoids, and quinones like thymoquinone, together with small quantity of alkaloids—all of that are good for reminiscence (Fontanet et al., 2021). Most of N. sativa’s pharmacological actions have been reported to be as a result of its energetic compounds thymoquinone, p-cymene, and α-thujene (Silva Andrade et al., 2021). Its alkaloids akin to nigellicine, nigellidine, and nigellimine have proven to cut back levels of cholesterol, therefore being probably helpful in opposition to cardiovascular illnesses (Asgary et al., 2018). Thymoquinone additionally confirmed comparable results by lowering complete ldl cholesterol, LDL-C, triglyceride [TG], and thiobarbituric acid (TBA)-reactive substance’s concentrations and rising the useful high-density lipoprotein ldl cholesterol (HDL-C) concentrations in animal fed with ldl cholesterol food regimen (Shabana et al., 2013). One of many prompt mechanisms for this hypolipidemia is the prevention of the de novo ldl cholesterol synthesis, whereas one other might be as a result of activation of bile acid secretion (Shabana et al., 2013). Equally, N. sativa has additionally diminished probabilities of aortic plaque formation immediately and not directly by way of controlling the inflammatory mediators launched by macrophages that take up LDL and kind foam cells’ preliminary stage in atherosclerosis (Shabana et al., 2013).

Then again, it has gained numerous significance as a result of its antidiabetic exercise when examined in rats and fewer generally on human topics the place each confirmed hypoglycemic outcomes (Shabana et al., 2013). The underlying mechanism is predicted that the N. sativa, and its elements are capable of maintain the beta cell integrity and regeneration of such cells, resulting in elevated insulin manufacturing (Shabana et al., 2013). Another explanations of the antidiabetic property prompt further pancreatic actions (unique of insulin launch) (Shabana et al., 2013) and reduce in hepatic gluconeogenesis (Srinivasan, 2018). In one other animal examine, it has reportedly inhibited intestinal absorption of glucose, in vitro and in vivo alongside inflicting insulin sensitization in skeletal muscle, adipose tissue, and liver by way of upregulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, peroxisome proliferator-activated receptor gamma (PPAR-ɣ), and rising the quantity of glucose transporter 4 (GLUT4) proteins (Viuda-Martos et al., 2010).

N. sativa can be helpful in treating inflammatory pulmonary responses. In a single such examine, it decreased iNOS (inducible nitric oxide synthase) exercise and elevated surfactant protein D when experimented on rats after pulmonary aspiration (Srinivasan, 2018). Furthermore, it additionally alleviated well being circumstances in sufferers with hyperoxia-induced lung harm and even bronchial asthma. Thymoquinone performs a task right here by the inhibition of the formation of leukotrienes that are potential inflammatory mediators in bronchial asthma, therefore enhancing chest wheezing, pulmonary perform checks, and different bronchial asthma signs (Srinivasan, 2018). Moreover, checks carried out on guinea pigs demonstrated antitussive exercise of N. sativa that was comparable with codeine (Maideen, 2020). Topics uncovered to aerosols of N. sativa and codeine had fewer coughs than these uncovered to saline. Thymoquinone was predicted to exert such an impact by way of opioid receptors since pretreatment of topics utilizing 2 mg/kg naloxone (opioid antagonist) blocked such antitussive impact (Maideen, 2020).

2.2 Indian pennywort (Centella asiatica L. city sys.)/Gotu Kola/Thankuni

Gotu Kola falls within the genus Centella (Syn. Hydrocotyle) of Apiaceae household (beforehand referred to as Umbelliferae) and subfamily Mackinlayoideae. It’s a plant that has the status to heal irregular metabolic circumstances in folks medication, particularly within the Ayurvedic system. Extract of Centella asiatica has been examined in opposition to endocrine illnesses like weight problems, osteolytic bone illnesses and kind 2 diabetes (Rameshreddy et al., 2018; Wang et al., 2019). These causes led us to pick out this useful meals to fight the put up COVID-19 problems in sufferers with diabetes. Essentially the most important bioactive elements of C. asiatica have been categorized into main collections, which contained triterpenoids saponins and their aglycones correspondents (asiaticoside, madecassoside, asiatic acid, and madecassic acid), and pectin, risky oil, traces of alkaloids, and others (Hashim et al., 2011). Triterpenes are the perfect bioactive chemical elements accountable for pharmacological exercise. Asiaticoside, Asiatic acid, Madecassoside, and Madecassic acid are the most typical of them (Inamdar et al., 1996; Lv et al., 2018). Some pentacyclic triterpenoids together with asiaticoside, brahmoside, and madecassic acid, together with different constituents as an example centellose, centelloside, and madecassoside are additionally bioactive compounds of C. asiatica. Solar et al. (2020) acknowledged of their assessment examine that Madecassoside, Asiaticoside, Madecassic acid, and Asiatic acid are broadly distributed within the physique, whereas Madecassoside and Asiaticoside could exert their organic exercise by means of conversion into aglycone (Madecassic acid and Asiatic acid) (Solar et al., 2020). They concluded these traits of compounds with the assistance of the experiments performed by different researchers (Solar et al., 2020). Many in vitro, in vivo, and likewise in silico research have been carried out to analyze the antidiabetic exercise of it. Ethanol extract of C. asiatica has given extremely propitious hypoglycemic exercise as its extract inhibited absorption of glucose by inhibition of each intestinal disaccharidase enzyme and α-amylase 1 (Berawi et al., 2017; Kabir et al., 2014). Fitrawan et al carried out in vitro experiment on C. asiatica fraction with the mix of Andrographis paniculata herb fraction and located that 10 and 30 μg/ml concentrations, respectively, have been capable of enhance insulin-stimulated glucose uptake (Fitrawan et al., 2018). Evaluation of the antidiabetic exercise of ethyl acetate (EtOAc) extract fraction and remoted compounds have been carried out in opposition to yeast α-glucosidase. Yeast α-glucosidase enzyme from S. cereviseae might be categorized as α-glycosidase sort and therefore was chosen for normal screening of α-glycosidase inhibitors. Additional investigation revealed that kaempferol and quercetin are probably the most energetic inhibitors (Dewi & Maryani, 2015). Chauhan et al confirmed with their in vivo examine on alloxan-induced rats with diabetes utilizing methanolic and ethanolic extracts that this herb has important antihyperglycemic exercise (Chauhan et al., 2010). Antioxidant potential of C. asiatica has been reported in lots of research (Zainol et al., 2003), and this impact is expounded to the hypoglycemic mechanism of this meals. So, triterpene compounds perform in opposition to diabetes mellitus by lowering the oxidative stress and facilitating the anti-inflammatory exercise. Antioxidative exercise of the extracts was measured utilizing the ferric thiocyanate technique and TBA check. The antioxidative actions have been then in contrast with that of α-tocopherol (pure antioxidant) and butylated hydroxytoluene or BHT (artificial antioxidant). The antioxidant exercise of Centella extract was evaluated by measuring its means to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals (Hashim et al., 2011; Mensor et al., 2001). Hashim et al. (2011) in contrast with different pure antioxidants, Centella confirmed higher antioxidant results than a fantastic grape seed extract.

2.3 Fenugreek (Trigonella foenum-graecum L)

Fenugreek (Trigonella foenum-graecum L) is a 20–130 cm lengthy, straight, not often ascending, annual legume plant. Seed is the half that’s used and might be rectangular to rounded (Petropoulos, 2002). It falls within the Rosaceae order, Legouminosae household, subfamily Papilionacea, and is distributed in Iran, India, Egypt, Pakistan, Algeria, Turkey, and Saudi Arabia. From the info of historic instances, spiritual scripture, journey information and anecdotes belonging to totally different continents and from totally different intervals of human historical past, a spread of medicinal properties have been acknowledged. Egyptian conventional medication, Chinese language conventional medication, and Ayurvedic medicines have been extensively utilizing this for making their formulations (Morcos et al., 1981; Yoshikawa et al., 1997). Romans used it to facilitate labor and ship, whereas in Chinese language medication fenugreek seeds are thought-about tonic in addition to a remedy for weak point and legs edema (Patil et al., 1997; Yoshikawa et al., 1997). Many pharmacological actions have been reported on fenugreek, experimented by many researchers. Fenugreek seeds are identified to be efficient in opposition to cardiovascular issues. Its lipid-lowering exercise makes this a possible useful meals in opposition to cardiovascular illnesses. It could decrease the extent of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) within the blood; consequently, it’s efficient in combating hypercholesterolemia (Ribes et al., 1987; Sharma, 1984). Lively compound diosgenin in fenugreek was noticed to indicate important hypercholesteremic exercise in vitro and in vivo research (Malinow, 1985; Malinow et al., 1978). Olfa Belguith-Hadriche and his staff (2013) studied methanol and ethyl acetate extracts of fenugreek and concluded that the flavonoids in fenugreek might be accountable for the hypercholesteremic exercise (Belguith-Hadriche et al., 2013; Hernandez-Galicia et al., 2002). Fenugreek additionally exhibits hypoglycemic exercise claimed by many researchers. They have been useful in attaining good glycemic management in sort 2 diabetes (Bouyahya et al., 2020; Büyükbalci & El, 2008; Capetti, 2020; Hernandez-Galicia et al., 2002). Animal research additionally clarify antidiabetic exercise of fenugreek. Fenugreek powder, suspension, decoction, and even oil fraction confirmed good antidiabetic exercise on diabetic animals’ in vivo (Ajabnoor & Tilmisany, 1988; Khosla et al., 1995; Madar, 1984; Mishkinsky et al., 1974; Ribes et al., 1986).

Ben-Arye et al. (2011) experimented on fragrant herbs for the ailment of higher respiratory tract issues and noticed peppermint spray was displaying important results (Ben-Arye et al., 2011; Schilcher, 2000). They might be helpful to fight frequent chilly and different respiratory tract issues which have been exhibited in vitro research (Ács et al., 2016; Fabio et al., 2007; Li et al., 2017). Animal research present that Mentha piperita is antispasmodic to tracheal easy muscle (de Sousa et al., 2010), stimulates chilly receptors (Shah & Mello, 2004), and exhibits antitussive impact on guinea pigs (Laude et al., 1994). Compound of M. piperita, Menthol confirmed therapeutic impact on capsaicin and neurokinin A induced airway restriction plus helped in stress-free potassium chloride (KCl) and acetylcholine induced bronchoconstriction ex vivo.

2.4 Fish oil

Lately, fish oil dietary supplements have been promoted as health-protective in numerous illnesses. Folks with extra fish consumption of their food regimen reported lesser incidences of stiffening of arterial partitions, platelet aggregation in blood circulation, atherosclerosis, and coronary coronary heart illnesses following that (Kundam et al., 2018). Even sufferers who already developed cardiovascular problems have been benefited from a small inclusion (150 g) of fish consumption, stopping additional problems (Kundam et al., 2018). Fish oil dietary supplements in food regimen, following ischemia reperfusion (IR) harm additionally alleviated modifications related to it- for instance decreased cardiac contraction drive, elevated coronary perfusion stress, ventricular arrhythmia, and launch of creatine kinase and thromboxane B2 (Kundam et al., 2018). As we all know, fish is a useful meals with plentiful minerals, nutritional vitamins, proteins, and important fatty acids. Fish oil from the liver, accommodates vitamin A, vitamin D, omega 3 polyunsaturated fatty acids (PUFAs) like eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid, and plenty of extra bioactive compounds accountable for the aforementioned well being advantages (Kundam et al., 2018; Sidhu, 2003). Furthermore, the cardiovascular illnesses are related to elevated plasma ldl cholesterol, LDL, triglycerides, raised blood stress together with decreased ranges of HDL, whereas the omega-3 PUFAs in fish oil (primarily EPA and DHA) have proven to decrease blood stress and viscosity. They might additionally trigger slight elevation of HDL2 ranges, therefore lowering the general dangers of coronary coronary heart illness (Kundam et al., 2018). Following the management of triglyceride ranges and hypertension in a affected person, omega-3 PUFAs are additionally capable of cut back probabilities of insulin resistance and therefore diabetes mellitus (Kundam et al., 2018; Sidhu, 2003). One other examine confirmed that 150 g of salmon consumption for thrice in every week, led to discount of C-reactive protein, IL-6 and prostaglandins that are inflammatory markers, therefore enhancing immune perform (Sidhu, 2003). Incidence of bronchial asthma and allergic reactions may even lower on consuming adequate fish meals (Kundam et al., 2018).

2.5 Garlic (Allium sativum)

Allium sativum has been cultivated worldwide and utilized in diversified methods in numerous nations for 1000’s of years (Beato et al., 2011). A. sativum usually named as (Rashun in Bengali) falls within the household of Alliaceae and plant order Liliales (Rocio & Rion, 1982). It’s usually well-known for its culinary use in lots of elements of the world, particularly in Asia. Garlic is an erect, monocot, and bulbous crop, which is named a perennial plant that’s sterile and propagates asexually as a result of it doesn’t produce seeds, thus referred to as a diploid plant (Benke et al., 2018; Mayer et al., 2013; Rocio & Rion, 1982). Garlic has the status of being a standard treatment as an antihypertensive agent. Garlic is being utilized by the normal healers of many nations as a prophylactic in addition to for making their folks medication in opposition to a wide range of illnesses (Duke & Ayensu, 1985). Its compounds have been investigated in opposition to hypertension and a sulfur compound alliin (S-allyl cysteine sulfoxide) confirmed important antihypertensive impact in addition to additionally elevated the efficacy of different cardioprotective brokers like captopril (Duke & Ayensu, 1985). It could inhibit the Squalene Monooxygenase enzyme by binding with vicinal sulfhydryl a part of the enzyme and cut back ldl cholesterol manufacturing (Gupta & Porter, 2001). Garlic oil confirmed hypolipidemic impact in rats fed a high-fat food regimen (Gupta & Porter, 2001; Yang et al., 2018). Platelet aggregation is a noteworthy reason for heart problems, and garlic can suppress mixture formation in many alternative pathways, thus could be thought-about as a greater cardioprotective agent (Isensee et al., 1993; Mukherjee et al., 2009; Rahman, 2007).

In vitro experiments proved that 4 compounds of garlic particularly allyl cysteine, alliin, allicin, and allyl disulfide have antioxidant properties and exhibit safety in opposition to free radical scavenging (Wang et al., 2016) for being antioxidant (Yang et al., 2001). One other work demonstrated that six organosulfur compounds (DAS, diallyl sulfide; DADS, diallyl disulfide; SAC, S-allylcysteine; SEC, S-ethylcysteine; SMC, S methylcysteine; SPC, S-propyl cysteine) derived from garlic hinder additional oxidative and glycative deterioration of partially oxidized and glycated LDL or plasma that’s efficient in opposition to diabetes-related vascular illness (Asdaq & Inamdar, 2010; Huang et al., 2004). Vital truth is that home-cooked garlic additionally retains the antioxidant exercise of it (Locatelli et al., 2017). As garlic has an excellent antioxidant property that hyperlinks it with its antidiabetic exercise. Phenol-rich garlic extract is discovered to be potent hypoglycemic agent (Akolade et al., 2019). Garlic when taken together with metformin (a hypoglycemic drug, which exhibits exceptional lower in fasting blood glucose stage and LDL stage in sufferers with sort 2 diabetes) (Chhatwal, et al., 2012). Ldl cholesterol stage could be managed by modifying one’s food regimen with garlic. Research present that garlic might be used to decrease the ldl cholesterol stage (Kamanna & Chandrasekhara, 1984; Kannar et al., 2001). However exactly, the important oil of garlic was examined for ldl cholesterol decreasing impact and confirmed many of the hypocholesterolemic impact comes from that portion (Kamanna & Chandrasekhara, 1984). Garlic lowers the LDL and will increase HDL within the rat mannequin (Aouadi et al., 2000). Garlic additionally exhibits synergistic impact with medication like glibenclamide (Poonam et al., 2013).

2.6 Ginger

Zingiber officinale belonging to the Zingiberaceae household and the Zingiber genus (Shahrajabian et al., 2019), is a standard spice of alternative on the subject of enhancing well being circumstances in sufferers with pulmonary fibrosis, pneumonia, acute respiratory misery syndrome (ARDS), sepsis, and plenty of inflammatory responses (Thota et al., 2020). It consists of loads of phenolic compounds, terpenes, lipids, and natural acids, out of which gingerols, shogaols, and paradols have gained lot of significance as bioactive compounds are accountable for helpful pharmacological results (Mao et al., 2019). Contemporary ginger is wealthy in gingerols like 6-gingerol, 8-gingerol and 10-gingerol, which later modifications into corresponding shogaols on warmth or storage (Mao et al., 2019). Ginger exerted cardioprotective results by rising the degrees of HDL-C immediately and not directly by rising apolipoprotein A-1 and lecithin-cholesterol acyltransferase mRNA within the liver, each being important a part of HDL formation (Mao et al., 2019). Along with that, ginger extract diminished physique weight, complete ldl cholesterol, and LDL in high-fat-diet rats, presumably as a result of expression of peroxisome proliferator-activated receptors (PPARα and PPARγ). Ginger additionally helped cut back blood stress in hypertensive rat fashions, whereas 6-shogaol elevated the variety of cells in G0/G1 section and activated Nrf2 and HO-1 pathways, therefore exerting antiproliferative results. ACE1 and arginase actions have been downregulated and NO upregulated, therefore inflicting vasodilation. Ginger was additionally stated to cut back platelet adenosine deaminase exercise and therefore enhance in adenosine ranges, which has proven to forestall platelet aggregation and trigger vasodilation in rats (Mao et al., 2019).

Ginger has performed an necessary function in controlling illness circumstances like diabetes not directly by way of administration of weight problems. Furthermore, each six shogaol and 6 gingerol inhibited the manufacturing of superior glycation finish merchandise that result in pathogenesis of diabetic problems like retinopathy, nephropathy, neuropathy, and cardiomyopathy (Mao et al., 2019). Six-paradol and 6-shogaol additionally prompted higher glucose utilizations in 3T3-L1 adipocytes and C₂C₁₂ myotubes by way of elevated phosphorylation of AMPK. Among the many many animal research carried out, they’ve proved helpful properties of 6-gingerol, which prompted glucose-stimulated insulin secretion, improved glucose tolerance in sort 2 diabetic mice by way of elevated glucagon-like peptide 1 (GLP-1) hormones, activated glycogen synthase 1, and elevated presence of glucose transporter sort 4 (GLUT 4) to trigger extra glycogen storage in skeletal muscle mass (Mao et al., 2019). General, bioactive constituents of ginger have proven to be antidiabetic for sufferers maybe not by reducing the extent of insulin however rising the sensitivity of it (Mao et al., 2019). By way of respiratory problems, ginger’s constituents—6-gingerol, 8-gingerol, and 6-shogaol have proven to calm down the airway easy muscle in each guinea pig and human trachea fashions. Attainable explanations of the impact might be attenuation of airway resistance in mice, as a result of discount of Ca²⁺ inflow attributable to 8-gingerol and one other might be as a result of suppression of phosphodiesterase 4D in people (Mao et al., 2019). Sufferers with allergic bronchial asthma signs and even ARDS, which additionally occur to be frequent incidences in sufferers with COVID-19 (Silva Andrade et al., 2021; Thota et al., 2020), have been benefited from ginger-rich food regimen the place its constituents improved gaseous trade in lungs and prevented alveoli abnormalities, wall thickening, infiltration of multinucleated cells and pneumocytes, lung cell proliferation, and even fibrosis. In a examine, 32 ARDS sufferers have been in contrast with placebo, the place 120 mg of ginger extract has elevated the tolerance of enteral feeding, diminished nosocomial pneumonia, and even diminished variety of days requiring exterior air flow in ICU (Thota et al., 2020). Citral and eucalyptol in ginger oil additionally efficiently inhibited tracheal contraction in rats when induced by carbachol (Mao et al., 2019). Zingerone in ginger has proven to cut back pulmonary fibrosis, fibrosis marker, hydroxyproline, oxidative stress marker, and malondialdehyde. As an alternative, diminished glutathione, superoxide dismutase, and glutathione peroxidase (GSH-Px), and so on., antioxidant markers within the lungs have been elevated in rats pretreated with bleomycin. As we all know, sufferers with COVID-19 face hyperinflammatory reactions, it is usually important to notice that constituents of ginger have been profitable in lowering TNF-α, IL-β, and kidney harm markers (KIM-1) (Chhatwal et al., 2012).

2.7 Bitter melon (Momordica charantia L)

Momordica charantia L. (bitter melon) is seen in tropical areas exactly in India, China, East Africa, and Central and South America and normally cultivated as a vegetable (Walters & Decker-Walters, 1988). Essentially the most used elements of M. charantia are fruits, leaves, and roots, which have been extensively utilized in Ayurveda and conventional Chinese language medication in opposition to many illnesses, as a bitter stomachic, laxative, anthelmintic, antidiabetic, jaundice, stones, kidney, liver, fever (malaria), eczema, gout, fats loss, hemorrhoids, hydrophobia (Ahmad et al., 2016; Begum et al., 1997). The fruit tastes bitter because the identify recommend and, the palatability of this vegetable is named “an acquired style.” This has been utilized in diabetes mellitus (Baldwa et al., 1977; Krawinkel & Keding, 2006). It has an excellent proportion of nutritional vitamins, minerals, flavonoids, and phenolic compounds (de Melo et al., 2000; Horax et al., 2005). Different bioactive compounds like saponins, peptides, and alkaloids are additionally current in addition to seeds include important oils (de Melo et al., 2000. Bitter melon has the status for being a possible antidiabetic and hypoglycemic plant in lots of conventional medicines and that attracted researchers to analyze its exercise to get exact knowledge of its exercise. In vitro and in vivo research present fairly good outcomes for non-insulin-dependent diabetes mellitus (NIDDM, sort II) and insulin-dependent diabetes mellitus (sort I) (Ahmad et al., 2012; Beloin et al., 2005; Grover & Yadav, 2004). Leatherdale et al. (1981) run an experiment in 9 Asian NIDDM outpatients, which concluded bitter melon juice consumption in glucose load prompted important enchancment in glucose tolerance with out rising the insulin ranges within the blood (Leatherdale et al., 1981). Srivastava et al. (1993) confirmed that it has a power impact on NIDDM as 3–7 weeks of consumption of dried fruit prompted noteworthy fall in postprandial blood glucose ranges. In addition they confirmed that the aqueous extract of bitter melon prompted a major fall in blood and urine sugar stage inside 7 weeks of time (Leatherdale et al., 1981; Srivastava et al., 1993) investigated on the seed oil of M. charantia, and it prompt that it’s a potent antidiabetic agent, with the assistance of α-glucosidase and α-amylase inhibition assays. Their examine exhibits that seed oil causes inhibition of α-glucosidase greater than α-amylase. From in vitro examine performed by Cumming and Hundal, it’s seen that the recent juice of the plant causes important enhance within the uptake of amino acids within the skeletal muscle and likewise elevated glucose uptake in L6 myotubes (Cummings et al., 2004). Different researches on the aqueous and chloroform extracts additionally confirmed elevated glucose uptake and upregulated GLUT-4, PPAR-γ, and phosphatidylinositol-3 kinase (PI3K) in L6 myotubes (Kumar et al., 2009). One other examine on the adipose cell 3T3-L1 was carried out to analyze glucose uptake and adiponectin secretion and concluded that the water-soluble a part of the plant elevated the glucose uptake at suboptimal concentrations of insulin in 3T3-L1 adipocytes (Meir & Yaniv, 1985). In vitro and in vivo pharmacological research describe that bitter melon extracts and bioactive compounds facilitate the regulation of glucose uptake (Meir & Yaniv, 1985; Roffey et al., 2007) stimulation of insulin secretion from pancreatic cells (Keller et al., 2011), stop pancreatic β-cells from inflammatory circumstances, show insulin mimetic actions, and cut back lipid accumulation in adipocytes (Popovich et al., 2010). In vivo research on animal fashions additionally present antihyperglycemic exercise. Aqueous, alkaline, and chloroform extracts of bitter melon in regular mice reduce the glycemic response of each oral and intraperitoneal glucose load (Day et al., 1990). Ali, Khan, and colleagues investigated pulp juice, and their outcome depicts lowered fasting blood glucose and glucose intolerance in NIDDM mannequin rats (Ali et al., 1993). In a while Srivasta et al. confirmed blood sugar stage had fallen after 3 weeks of remedy with aqueous extract of bitter melon in alloxan-induced diabetic rats (Srivastava et al., 1993). The extract additionally improved glucose intolerance in streptozotocin (STZ)-treated diabetic rats and elevated the glycogen synthesis within the liver (Sarkar et al., 1996). Virdi, Sivakami, and staff administered 20 mg/kg physique dose of recent unripe fruits, in rats and noticed 48% diminished fasting blood glucose, which was just like glibenclamide, a widely known oral antidiabetic drug (Virdi et al., 2003). Dose-dependent hypoglycemia in regular (normoglycemic) and streptozotocin (STZ)-treated diabetic rats was noticed by the administration of the entire plant extract (Ojewole et al., 2006). Different research described that M. charantia extract enhanced insulin sensitivity, glucose tolerance, and insulin signaling in high-fat diet-induced insulin resistance rats (Sridhar et al., 2008) and likewise levelled up the conventional glucose focus in power sucrose-loaded rats (Chaturvedi & George, 2010). Some research prompt bitter melon juice might be used as an antidiabetic treatment through the use of them by means of crushing and straining the unripe fruit and brought a couple of times a day. They may also be taken as a decoction or “tea” (sizzling water extract) of the aerial elements of the vegetation, free of huge fruit (Bailey et al., 1986). The immature fruits of M. charantia could be ready in some ways. Furthermore, they may also be dehydrated, pickled, or canned and might be blanched or soaked in salt water earlier than cooking to cut back the bitter style (Grover & Yadav, 2004).

2.8 Peppermint (Mentha piperita L)

M. piperita L belongs to the Lamiaceae household (mint household) and is a perennial, glabrous, and strongly aromatic herb. This is named peppermint and is native to Europe, discovered within the northern USA and Canada, and cultivated in lots of elements of the world (McKay et al., 2006). Temperate and subtropical areas have been the zone for cultivation for greater than 1,000 years (Benabdallah et al., 2018). The listing of purported advantages and makes use of of peppermint as a folks treatment or in complementary and various medical remedy embrace the next: biliary problems, dyspepsia, enteritis, flatulence, gastritis, intestinal colic, and spasms of the bile duct, gallbladder, and GI tract (Mahendran & Rahman, 2020; McKay et al., 2006). Its leaves are used as carminatives and for gastric issues. They’re additionally used as stimulants, in vomiting, liver issues and gallbladder an infection. Conventional makes use of have been reported in lots of varieties. In vivo and in vitro research have been performed extensively to grasp its pharmacological exercise. An antibacterial examine on respiratory tract pathogens Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus performed by Inouye et al. (2001). They used modified dilution assays and additional which confirmed that peppermint oil has important impact on respiratory tract infections and prompt that menthol and menthone are the simplest compounds (Bahl et al., 2000; Inouye et al., 2001) together with different terpene molecules (Phatak & Heble, 2002). The same experiment was performed by (Furuhata et al., 2000). They estimated time-course modifications within the bacterial rely of L. pneumophila within the extract options of peppermint and located that the bacterial rely turned undetectable after 3–12 hr of peppermint remedy (Furuhata et al., 2000). In a while, many research additionally proved its exercise in opposition to respiratory tract pathogens (Ács et al., 2016; Ács et al., 2018). One other important compound of peppermint is 1,8-cineole 200 mg dose of which diminished the treatment price to 36% for asthmatic sufferers who have been taking prednisolone (Juergens et al., 2003). It confirmed good anti-inflammatory exercise (Juergens et al., 2003). Morice et al. defined peppermint oil as antitussive agent (Morice et al., 1994). M. piperita can be identified to have antispasmodic exercise, which was noticed on rat trachea involving prostaglandins and nitric oxide synthase by de Sousa and his staff (de Sousa et al., 2010). From the research of conventional medication, it was depicted that M. piperita has been broadly used for respiratory tract illnesses. Its leaves, infusions, or important oil was once good expectorant and anticongestive (Morice et al., 1994). Newest examine on peppermint performed by Cam, Basyigit, and staff with powdered peppermint extract, which proved that it’s potent antidiabetic and antihypertensive useful meals. Eriocitrin is a dominant phenolic compound, and (Cam et al., 2020) antidiabetic and antihypertensive actions have been evaluated by the diploma of inhibition of (α-glucosidase) and angiotensin 1-converting enzyme, ACE, respectively.

2.9 Turmeric (Curcuma Longa L.)

Turmeric (Curcuma longa L.) is a useful meals belonging to the Zingiberaceae household and is a spice that has been an important a part of cooking Asian delicacies and in conventional medication like Ayurveda (Niranjan & Prakash, 2008), Unani and Chinese language medicines for hundreds of years (Niranjan & Prakash, 2008). Its bioactive compounds are mainly phenols, terpenes, sterols, and alkaloids in nature (Emirik, 2020). Curcumin in turmeric is a phenol that has good hopes to be used in sufferers with COVID-19 because it has beforehand been efficient in opposition to influenza A virus, HIV, enterovirus, 71 (EV71), herpes simplex virus and even inhibited the replication of SARS-CoV and inhibited 3 Cl protease in Vero E6 cells when examined (Babaei et al., 2020). By way of enhancing put up COVID-19 problems, curcumin and tetrahydro curcumin have proven to cut back blood sugar and glycosylated hemoglobin ranges in rats, therefore proving to be antidiabetic (Niranjan & Prakash, 2008). Turmeric additionally diminished oxidative stress as a result of lower of glucose within the polyol pathway resulting in elevated NADPH/NADP ratio and elevated GSH-Px exercise, which is an antioxidant enzyme (Mao et al., 2019). Turmeric may additionally be helpful due to its means to cut back the degrees of circulating inflammatory mediators like IL-6 and TNF-α, cytokines, chemokines, bradykinin, remodeling development factor-beta-1 (TGF-β1), cyclooxygenase (COX), plasminogen activator inhibitor-1 (PAI-1), IL-17A, and caspase-3 (Cas-3) (Babaei et al., 2020; Locatelli et al., 2017). Most significantly, it could goal the proinflammatory NF-κB pathway, therefore defending in opposition to acute lung harm and ARDS, generally seen in sufferers with COVID-19. Curcumin additionally inhibits the exercise of bradykinin, therefore suppressing coughs induced by it. Furthermore, it decreased interstitial fibrosis and bronchoconstriction. Curcumin may additionally delay fibrosis development by inhibiting the synthesis of collagen and procollagen I mRNA, thus reducing collagen deposition present in pulmonary fibrosis (Madar, 1984). Turmeric extract (1.5, 3 mg/ml) has proven to cut back tracheal contraction induced by ovalbumin and confirmed most response to methacholine in rats (Babaei et al., 2020). Capsule Curcumin 500 mg BD improved pressured expiratory quantity (FEV1) as compared with normal remedy for bronchial asthmatic sufferers when taken day by day for 30 days (Babaei et al., 2020). Therefore, it’s potential in enhancing put up COVID-19 respiratory signs and problems stay notable.

3.1 Number of useful meals sources

The 9 useful meals particularly black cumin, Indian pennywort, fenugreek, fish oil, garlic, ginger, bitter melon, peppermint, and turmeric have been shortlisted due to the constructive results they possess in ameliorating cardiac, diabetic, and respiratory problems which are frequent in sufferers of put up COVID-19 survival. It was additionally taken under consideration that the above chosen meals have been reasonably priced and available for consumption by the mass inhabitants, even in creating nations like Bangladesh. Then bioactive compounds in these meals have been listed, as many as attainable primarily based on in depth analysis and literature search.

3.2 Library preparation and ADME examine

A library of 266 bioactive compounds current within the chosen useful meals has been ready. Compounds have been downloaded from the “PubChem” and “Chemspider” database, and the library was compiled. Duplicate compounds have been deleted. Compounds have been subjected to ADME evaluation. We used the webserver SwissADME (Daina et al., 2017) to research the absorption, distribution, metabolism, and elimination properties of the compounds. Furthermore, drug likeness properties have been evaluated by analyzing the variety of H-bond acceptor, H-bond donator, solubility class, and Lipinski’s rule of 5 standards (Barret, 2018).

3.3 Main digital screening by way of molecular docking for community pharmacology examine

After ADME screening, these compounds have been subjected to molecular docking evaluation and community pharmacology research utilizing the next methodological approaches.

3.4 Bioinformatics-based community pharmacology

3.5 Redocking of the goal compounds

Among the many finest genes chosen from community pharmacology examine, some targets have been chosen, which have been associated to cardiovascular illnesses, diabetes and respiratory problems. These targets have been ready the identical manner as defined within the Sections 3.3.1 and three.3.2 adopted by molecular docking evaluation. After docking, 3D and 2D complexes have been visualized within the protein plus internet server (https://proteins.plus).

4.1 ADME and pharmacokinetic properties

In complete, 139 compounds handed our standards chosen for ADME examine and pharmacokinetic properties (Desk 1). Because the meals will likely be immediately consumed, they need to be correctly absorbed within the GI tract. Therefore, compounds with excessive GI absorption price have been chosen. Bioavailability can be necessary to know if the compounds are current in systemic circulation or not. Compounds with a bioavailability of higher than 0.55 have been chosen as candidates. Solubility is necessary to make sure the distribution of the constituents by way of the systemic circulations into the goal tissues and the compounds having excessive to average solubility have been chosen. Molecular weight, variety of H-bond donor, and H-bond acceptor are the structural parameters, which have been in acceptable limits.

4.2 Main digital screening by way of molecular docking for community pharmacology examine

From the first screening of compounds for community pharmacology research, we bought 71 compounds that confirmed good binding affinity of “−7” or higher for the respective goal proteins that have been carried ahead for reconfirmation by way of community pharmacology research (Desk 2 and 3).

4.3 Community pharmacology

4.3.1 Identification of goal proteins

We recognized 636 goal proteins (Desk S1) utilizing STITCH and 604 goal proteins (Desk S2) utilizing SwissTargetPrediction. After overlapping by the Venn device, we bought 159 frequent goal proteins (Determine 1), and 159 goal proteins are tabulated in Desk S3.

4.3.2 Development, evaluation of goal proteins’ protein–protein interplay community, and identification of hub nodes

Frequent goal proteins have been set to STRING-DB v11.0 for the development of PPI. We discovered that 159 goal proteins are concerned in PPI (besides STK17B). Then the interplay of STRING was inputted in 3.6.1 software program to assemble a PPI community. The highest 20 hub nodes primarily based on the utmost diploma of interplay are displayed in Determine 2.

Moreover, we recognized the rank of interacted goal proteins by making use of Cytoscape plugin cytoHubba as proven in Determine 3 (Chin et al., 2014). Most interplay levels point out the potential organic features. The rank of the highest 23 goal proteins on the premise of the diploma of interplay is proven in Desk 4 (Szklarczyk et al., 2019). All of the goal proteins are tabulated in Desk S3. AKT1, with 99 levels of interplay, was positioned within the prime place. Then the interplay of STRING was put into 3.6.1 software program to assemble a PPI community.

TABLE 4.
Prime 23 hub nodes recognized primarily based on diploma of interactions

Rank	Title of goal genes	Diploma of interactions	Interacting compounds
1	AKT1	99	Apigenin, betulinic acid, curcumin, kaempferol, luteolin, quercetin, gallic acid, demethoxycurcumin, laricytrin, nigellidine, tricin
2	IL6	91	Catechin, curcumin, epicatechin, quercetin, Asiatic acid, diosgenin, yamogenin
3	MAPK3	87	Apigenin, betulinic acid, curcumin, kaempferol, quercetin, gingerol, 6-gingerol
4	VEGFA	86	Apigenin, curcumin, diosgenin, quercetin, naringenin
5	EGFR	83	6-Dehydrogingerdione, apigenin, curcumin, demethoxycurcumin, hymecromone, kaempferol, laricytrin, luteolin, quercetin, tricin, betulinic acid
6	CASP3	82	Gallic acid, sitosterol, thymoquinone, quercetin, luteolin, kaempferol elemene, curcumin, betulinic acid, apigenin, 6-shogaol, medicarpin
7	MAPK1	82	Medicarpin, nigellone, eicosapentaenoic acid, dithymoquinone, diosgenin, 6-shogaol, 6-dehydrogingerdione, apigenin, betulinic acid, curcumin, kaempferol, luteolin, naringenin, quercetin, caffeic acid
8	TNF	82	6-Gingerol, 6-shogaol, apigenin, curcumin, diosgenin, gingerol, hymecromone, kaempferol, luteolin, medicarpin, naringenin, quercetin, stigmasterol, eicosapentaenoic acid, demethoxycurcumin, gingerenone-A, madasiatic acid, madecassic acid
9	SRC	78	6-Dehydrogingerdione, 6-gingerol, 6-shogaol, apigenin, dithymoquinone, gingerol, kaempferol, laricytrin, luteolin, medicarpin, naringenin, nigellone, paradol, quercetin, tricin
10	STAT3	73	Curcumin, kaempferol, luteolin, demethoxycurcumin, dithymoquinone, docosahexaenoic acid, nigellone, paradol
11	MAPK8	73	Dithymoquinone, curcumin, diosgenin, luteolin, quercetin, caffeic acid
12	HSP90AA1	70	Luteolin, curcumin, 6-dehydrogingerdione, 6-gingerol, dithymoquinone, gingerenone-A, gingerol, nigellone, paradol
13	ESR1	70	Apigenin, kaempferol, quercetin, 6-gingerol, 6-shogaol, alpha-eudesmol, gingerol, hymecromone, kaempferol, luteolin, medicarpin, naringenin, nigellidine, paradol, sitosterol, stigmasterol, tricin
14	PTGS2	68	Apigenin, catechin, curcumin, diosgenin, quercetin, thymoquinone, eicosapentaenoic acid, docosahexaenoic acid, asiatic acid, betulinic acid, kaempferol, luteolin, madecassic acid, madasiatic acid
15	MTOR	68	Curcumin, luteolin, 6-dehydrogingerdione, 6-gingerol, 6-shogaol, demethoxycurcumin, gingerol, medicarpin, paradol
16	EP300	62	Curcumin, eicosapentaenoic acid, demethoxycurcumin
17	MAPK14	62	Naringenin, quercetin, 6-dehydrogingerdione, 6-shogaol, diosgenin, eicosapentaenoic acid, yamogenin
18	BCL2L1	59	Curcumin, luteolin, gallic acid, docosahexaenoic acid, eicosapentaenoic acid, naringenin
19	PPARG	58	Curcumin, luteolin, eicosapentaenoic acid, docosahexaenoic acid, 6-gingerol, Asiatic acid, betulinic acid, dithymoquinone, gingerol, madasiatic acid, naringenin, madecassic acid, paradol, sitosterol, stigmasterol
20	ERBB2	57	Curcumin, luteolin, 6-gingerol, gingerenone-A, gingerol, nigellidine
21	RELA	56	Curcumin, paradol
22	MMP9	55	6-Gingerol, apigenin, curcumin, gingerol, luteolin, quercetin, caffeic acid, gallic acid, 6-dehydrogingerdione, 6-shogaol, apigenin, dithymoquinone, docosahexaenoic acid, eicosapentaenoic acid, gingerenone-A, kaempferol, laricytrin, nigellone, tricin
23	MDM2	53	Curcumin, yamogenin

4.3.3 Gene Ontology evaluation of interacted goal proteins

GO enrichment evaluation of interacted goal proteins (complete 159) that work together with compounds was carried out by GSEA. The 159 goal proteins have been integrated into the GSEA and chosen people. All kinds of BPs (Desk S4), MFs (Desk S5), and CCs (Desk S6) have been recognized. The highest 10 BPs, MFs, and CC are proven in Determine 4.

4.3.4 Goal proteins’ set enrichment evaluation of KEGG pathway

To additional elucidate the connection between the goal proteins and the pathways, we recognized 97 KEGG pathways (Desk S7) that have been considerably related to the goal proteins. These pathways have been primarily concerned in most cancers, respiratory illnesses, diabetes, immune regulation, metabolisms, and different mobile and developmental signaling pathways as proven in Determine 5. These outcomes point out that these compounds could also be related to the enrichment of those pathways.

4.4 Redocking of the goal compounds

We chosen the perfect 5 targets that interacted with an excellent variety of compounds and have been strongly related to the illness pathogenesis and have an excellent diploma of interactions. MAPK-1, HSP90AA1, AKT1, PPARG, and TNF-alpha are the targets, and the compounds that confirmed interplay in community pharmacology examine have been subjected to molecular docking to research their binding affinity. For cardiovascular problems, HSP90AA1 (PDB ID: 1BYQ) and MAPK1 (PDB ID: 2Y9Q) have been chosen, whereas for diabetes PPARG (PDB ID: 1ZGY) and TNF-alpha (PDB ID: 5M3J) and for respiratory problems AKT-1(PDB ID: 1UNP) have been chosen.

4.4.1 Genes related to cardiovascular illnesses

Warmth shock protein (HSP90AA1) gene

This gene is expounded to cardiovascular illnesses. The interacting compounds have been luteolin, curcumin, 6-dehydrogingerdione, 6-gingerol, dithymoquinone, gingerenone-A, gingerol, nigellone, paradol. luteolin, and curcumin that proved to be the perfect compounds from docking outcomes (Desk 5).

TABLE 5.
Molecular docking rating of targets with their interacting compounds chosen after community pharmacology

Illnesses	Heart problems				Diabetes						Respiratory dysfunction
Genes	HSP90AA1 (1BYQ):		MAPK1 (2Y9Q)		PPARG1 (1ZGY)		TNF-Alpha (5M3J)				AKT1 (1UNP)
Goal	Compound	Binding affinity (docking rating)	Compound	Binding affinity (socking rating)	Compound	Binding affinity (socking rating)	Compound	Binding affinity (docking rating)	Compound	Binding affinity (socking rating)	Compound	Binding affinity (docking rating)
	Luteolin	−7.6	Quercetin	−9.1	Stigmasterol	−8.5	Stigmasterol	−9.3	Demothoxycurcumin	−7.8	Apigenin	−7.2
	Curcumin	−7.6	Luteolin	−8.9	Luteolin	−8.3	Diosgenin	−8.9	Tricin	−7.8	Luteolin	−7
	Nigellone	−7.2	Apigenin	−8.8	Naringenin	−8.3	Luteolin	−8.4	Madasiatic acid	−7.5	Nigellidine	−6.9
	Dithymoquinone	−6.8	Naringenin	−8.6	Sitosterol	−8.1	Laricytrin	−8.3	Gingerenone	−7.5	Quercetin	−6.7
	Gingerenone	−6.8	Medicaprin	−8.5	Curcumin	−7.7	Naringenin	−8.3	Madecassic acid	−7.4	Laricytrin	−6.7
	6-Dehydrogingerdione	−6.5	Dithymoquinone	−8.4	Madasiatic acid	−7.6	Apigenin	−8.2	Hymecromone	−6.9	Kaempferol	−6.5
	Gingerol	−5.9	Curcumin	−7.8	Dithymoquinone	−7.3	Quercetin	−8.1	6-Shogaol	−6.3	Tricin	−6.5
	Paradol	−5.7	6-Shogaol	−6.6	–	–	Kaempferol	−7.9	6-Gingerol	−6.2	Curcumin	−6.3
	–	–	–	–	–	–	Medicaprin	−7.9	Gallic Acid	−5.4	Gallic Acid	−5.6
	–	–	–	–	–	–	Curcumin	−7.8			Demethoxycurcumin	−5.5

Gingerol, curcumin, and luteolin additionally confirmed fairly good binding affinity of −7.2, −8.4, and 9.8, respectively, in main screening with cardiovascular goal TNNI3K. Therefore, these are hypothesized to be finest for cardiovascular problems. Interactions discovered from protein plus with goal genes are proven in 2D and 3D pictures (Determine 6).

Mitogen-activated protein kinase gene

The compounds that work together with mitogen-activated protein kinase (MAPK1) have been medicarpin, nigellone, EPA, dithymoquinone, diosgenin, 6-shogaol, 6-dehydrogingerdione, apigenin, curcumin, kaempferol, luteolin, naringenin, quercetin, and caffeic acid. Their docking outcome exhibits a binding affinity of “−7” and higher with goal MAPK1 (Desk 5). Quercetin, apigenin, and luteolin have been discovered to be the perfect as a result of they exhibited good nonbonded interactions with the goal (Determine 7).

4.4.2 Genes related to diabetes

Peroxisome proliferator-activated receptor gamma gene

Curcumin, luteolin, EPA, DHA, 6-gingerol, asiatic acid, dithymoquinone, gingerol, madasiatic acid, naringenin, madecassic acid, paradol, sitosterol, and stigmasterol have been the great interacting compounds from community pharmacology. They’re associated to antidiabetic exercise. Amongst these, stigmasterol, luteolin, and naringenin have been the perfect compounds from docking outcomes displaying binding affinity of −9.4, −9.7, and −9.4 in main screening (Desk 2). Two-dimensional (2D) and three-dimensional (3D) interactions of naringenin and luteolin complicated with protein are proven (Determine 8).

Tumor necrosis issue alpha (TNF–alpha) gene

Apigenin, 6-gingerol, 6-shogaol, curcumin, diosgenin, gingerol, hymecromone, kaempferol, luteolin, medicarpin, naringenin, quercetin, stigmasterol, EPA, demethoxycurcumin, gingerenone-A, madasiatic acid, and madecassic acid interacted with TNF-alpha (Desk 5). Fairly various compounds confirmed good binding affinity of −7 or higher in main screening as effectively. Stigmasterol, diosgenin, luteolin, naringenin, apigenin, quercetin, medicaprin, curcumin, tricin, muriatic acid, gingerenone, and medicassic acid have been the compounds exhibiting good docking outcome and nonbonded interplay from main screening (Desk 2). Amongst them, 2D and 3D interactions of naringenin and stigmasterol with goal gene TNF-alpha are proven depicting the nonbonded interactions (Determine 9).

4.4.3 Genes related to respiratory illnesses

Ak pressure remodeling (AKT1) gene

The results of community pharmacology exhibits 10 interacting energetic compounds with AKT1, particularly apigenin, curcumin, kaempferol, luteolin, quercetin, gallic acid, demethoxycurcumin, laricytrin, nigellidine, and tricin. Docking outcomes of AKT1 and interacting compounds present their binding affinity with protein. Luteolin, apigenin, and nigellidine confirmed finest outcomes with AKT1 having good nonbond interplay (Desk 5). Luteolin, apigenin, and nigellidine additionally considerably confirmed good molecular docking outcomes of −9.7, −9.5, and −9.4, respectively, in main screening (Desk 2). They might be useful for coping with respiratory tract issues. 2D and 3D interplay of AKT1 with luteolin and apigenin is represented displaying nonbonded interplay (Determine 10).

4.5 Chosen useful meals for every particular put up COVID-19 complication

Desk 6 summarizes the bioactive compounds that interacted with the genes chosen for cardiac, diabetes, and respiratory problems. The corresponding useful meals that accommodates the bioactive compounds can be tabulated to suggest the consumption of these particular meals for enhancing every of the put up COVID-19 complication. Our outcomes confirmed that luteolin, curcumin, nigellone, dithymoquinone, gingerenone, 6-dehydrogingerdione, gingerol, paradol, quercetin, apigenin, naringenin, medicarpin, and 6-shogaol interacted with HSP90AA1 and MAPK1 and have the potential to enhance cardiac problems in. Aforementioned compounds are current in our chosen useful meals like black cumin, Indian pennywort, fenugreek, garlic, ginger, and turmeric. Equally, stigmasterol, luteolin, naringenin, sitosterol, curcumin, madasiatic acid, dithymoquinone, diosgenin, laricytrin, apigenin, quercetin, kaempferol, medicarpin, demethoxycurcumin, tricin, gingerenone, madecassic acid, hymecromone, 6-shogaol, 6-gingerol, and gallic present in bitter melon, black cumin, Indian pennywort, fenugreek, garlic, ginger, and turmeric are probably helpful when it comes to mediating antidiabetic problems. Apigenin, luteolin, nigellidine, quercetin, laricytrin, kaempferol, tricin, curcumin, gallic acid, and demethoxycurcumin present in bitter melon, black cumin, Indian pennywort, fenugreek, garlic, ginger, and turmeric can alleviate respiratory problems of our concern.