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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5336_Библиотеки_им_академика_М_И_Перельмана

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296 Motahare Nayebzadeh etal.
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Study design
Double-blind
randomized, placebo-controlled clinical trial
Triple-blind
randomized, placebo-controlled clinical trial
Randomized, single-
blind, controlled, crossover feeding study
Double-blind,
randomized controlled trial
Randomized single-
blind, placebo­controlled trial
No. of patients Disease Plant(s) Part(s) Control group
46 Asthma Adiantum capillus-
Flower
Placebo 5 days Nighttime awakening
veneris
60 Moderate to
severe
Matricaria chamomilla Hyssopus officinalis Glycyrrhiza glabra Althaea officinalis Malva sylvestris Ziziphus jujuba Drimia maritima (L.)
Stearn
Aerial part Aerial part Root Flower Flower Fruit Bulb Placebo 6 weeks The syrup significantly
persistent asthma
25 CHD risk
factors such as inflammation and
D.A. Webb
Nut Cholesterol-
lowering control diet without nuts
hemostasis
128 Intermittent
Viola odorata L. Flower Placebo 5 days The syrup enhanced
asthma
400 Recurrent
tonsillitis and peritonsillar abscess
Viola odorata L. Flower Co-amoxiclav
(625 mg) and fexofenadine (60 mg) twice daily
Treatment duration Results
and severity of cough
improved FEV
1
6 weeks High-almond diet
significantly decreased serum E-selectin and almond diets can reduce CRP
In control and
high-almond diets, tPA antigen was significantly lower
cough suppression with short-acting β-agonist
7 days Decoction of V. odorata
flower (1 mg/150 ml water) can decrease the frequency of these abscesses in one year
Reference
Javid etal. (2019)
Nejatbakhsh etal.
(2017)
Rajaram etal.
(2010)
Qasemzadeh etal.
(2015)
Ali etal. (2013)
CHD, coronary heart disease; tPA, tissue plasminogen activator.
Cough Management 297
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important flavonoid compounds in A. capillus­veneris are quercetin, quercetin-3-O-rutinoside,
and quercetin-3-O-glycoside in the ethyl acetate fraction (Singh et al., 2008; Ibraheim
et al., 2011; Gaikwad-Samdani, 2012; Ishaq et al., 2014; Al-Snafi, 2015; Dehdari and Ha- jimehdipoor, 2018; Khan et al., 2018; Nazim etal., 2018; Zhang etal., 2019). In a study, the
antibacterial effect of the methanol fraction of A. capillus-veneris fronds against MDR bacterial strains was investigated, and the maximum zone of inhibition (ZI) against Klebsiella pneu-
moniae, Providencia, Shigella, Staphylococcus aur­eus, Vibrio cholerae, Salmonella typhi, and Proteus vulgaris was determined by the disk diffusion
method (Hussain eta l., 2014). In another study, the anti-inflammatory effect of ethanolic ex­tract of A. capillus-veneris in vitro using HEK293 and HepG2 cell lines and in vivo was investi­gated experimentally on 32 mice. The results showed that this extract could normalize p38 and nuclear factor-κB (NF-κB) activation in mice as well as the increase in spleen index by lipopolysaccharide (LPS) induction (Yuan etal.,
2013). In an in vivo study that aimed to compare the anti-asthmatic effect of the ethanolic ex­tract of A. capillus-veneris fronds with that of Sargassum wightii on 24 guinea pigs with acute asthma induced by histamine aerosol, it was found that A. capillus-veneris was more effective than the other plant (Kumar et al., 2012). Twen­ty-seven healthy rats were examined in hypoxia condition to investigate the Bcl2-associated-X protein (Bax)/B-cell lymphoma 2 (Bcl-2) apop­totic index ratio and remodeling of pulmonary epithelial cells in the control group compared to the group supplemented with a A. capillus- veneris ethanol extract obtained using the Soxhlet method. The result showed this extract could significantly modulate the apoptotic ratio (Yadegari etal., 2019). In another in vivo study, the anti-inflammatory activity of an alcoholic extraction of A. capillus-veneris was evaluated by inducing paw edema with formalin in 66 mice and nine rats. The results showed that this frac­tion could significantly inhibit the release of nitric oxide (NO) and tumor necrosis factor-α (TNF-α) (Haider et al., 2011). Another study examined the efficacy of aqueous and hydroal­coholic extracts of A. capillus-veneris in the prevention of inflammation and incidence of colitis. During this examination, 60 Wistar rats
were induced with colitis by rectal injection of acetic acid 3% w/w and the efficacy of two ex­tracts of A. capillus-veneris was compared to that of prednisolone and mesalazine. Results showed that these extracts have beneficial, dose­dependent, ulcer healing, anti-inflammatory, and antioxidant activities by suppressing inter­leukin-6 (IL-6), NO, and TNF-α release as well as inhibiting NF-κB activation (Khoramian etal., 2020).
Althaea officinalis L.
The secondary metabolites of Althaea offici­nalis include alkaloids, glycosides, flavonoids
(like isoscutellarein, kaempferol, hypolaetin, and luteolin), coumarines (like scopoletin), phenolic acids, terpenes, tannins, and sap­onins (Table 8.5). Mucilage of A. officinalis contains rhamnogalacturonan, glucans, ara­binans, and arabinoglucans (Gautam et al., 2015; Mahboubi, 2020).
In an in vitro study, the antibacterial ac­tivity of the essential oil and the petroleum ether, acetone, methanol, and aqueous ex­tracts of A. officinalis seeds was evaluated against various respiratory pathogens such as Haemophilus influenzae, Pseudomonas
aeruginosa, S. aureus, Streptococcus pneumoni­ae, and Streptococcus pyogenes by the agar
diffusion method. The results showed that both the essential oil and the seed extracts possess antimicrobial activity. In particular, the 200 mg/ml concentration of the essen­tial oil was more effective against S. pyogenes and H. influenza, and the methanol extract showed high antimicrobial activity against P. aeruginosa (Gautam etal., 2015).
Table 8.5. Major phytochemicals of Althaea officinalis seeds. (From Gautam etal., 2015.)
Extract Compounds
Methanol Alkaloids, flavonoids, glycosides,
terpenes, saponin, tannins Petroleum ether Alkaloids, steroids Acetone Alkaloids, terpenes, saponins,
tannins Aqueous Alkaloids, flavonoids, glycosides,
terpenes, saponins, tannins
298 Motahare Nayebzadeh etal.
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Cordia myxa L.
Major compounds of the extract obtained from Assyrian plum fruit include the essential oil, flavonoids, glycosides, sterols, carbohydrat es, terpenoids, saponins, alkaloids, coumarins, phenolic acids, mucilages, resins, tannins, and gums (Al-Snafi, 2016a; Shwaish and Imarah,
2017). Cordia myxa fruit extract contains high amounts of phenolic compounds, and the antitumor and antioxidant activities of this plant are related to the individual concentra­tions of these substances including gallic acid, catechin, caffeic acid, p-coumaric acid, rutin, quercetin, and kaempferol (El-Massry et al.,
2021). A study evaluated the mechanism of tracheal relaxation activity of alcoholic extracts obtained from C. myxa fruits in sheep tracheal muscle and showed this extract can induce the expression of NO synthesis, which is related to the cytosolic calcium ions (Ca
2+
) originating
from extracellular space (Al-Bayati, 2008).
The anti-inflammatory activity of the aqueous alcoholic extract of C. myxa fruit was evaluated by acetic acid and formalin assay in 72 mice. Tramadol and indometh­acin administered intraperitoneally and or­ally, respectively, were compared with this fruit extract. The study showed that hy­droalcoholic extracts of this fruit possess significant anti-inflammatory activity in both chronic and acute phases (Ranjbar etal., 2013). In another in vivo study, colitis was induced in 48 rats by intrarectal admin­istration of acetic acid to show the anti­inflammatory effect of the suspension of the section surrounding the seeds of C. myxa fruit, which have the largest amount of mucilage in the whole fruit. The results showed that this effect of C. myxa is related to the fix­ation of zinc (Zn), manganese (Mn), copper (Cu), and selenium (Se) in the destroyed tis­sue (Al-Awadi etal., 2001).
The immunomodulatory activity of C. myxa fruit was evaluated in 40 BALB/c (al­bino, laboratory-bred) mice through com­parison between immunization by hydatid cyst fluid antigens (HCFAg) and treatment by aqueous extract of the fruit in four mice groups, which revealed that this extract could stimulate the immune responses in mice and cell-mediated cases (Rashid Ali
etal., 2015). In another study, the antican­cer and anti-inflammatory activity of hy­droalcoholic extracts of C. myxa fruit was investigated through inhibition of cyclooxy­genase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymes with the molecular docking of α-amyrins as a triterpenoid of C. myxa and both enzymes. These enzymes are related to occurrence of cancer, so this extract can inhibit cancer pathways in the lung, breast, and colon neoplasm (Ranjbar etal., 2016).
Commiphora myrrha (Nees) Engl.
Commiphora myrrha or true myrrh from the family Burseraceae has long been used as a medicinal plant. It is a gum-resin that is ex­tracted from the bark of the trees of Commi- phora species (Shen et al., 2012). Ethanol and ether extracts of C. myrrh have been traditionally used in Greece to treat cough, wounds, sepsis, and mouth infections. In Britain, the resin has traditionally been used to treat cough, gingivitis, tonsillitis, pharyn­gitis, sinusitis, ulcers, and skin inflamma­tion (Shen et al., 2012). As mentioned in Chinese culture, the extract of C. myrrha showed activity against cancer diseases such as lung cancer. Due to its anti-inflammatory, antioxidant, antibacterial, and expectorant properties, C. myrrha it is also used to cure chest infections and sore throat. Further­more, furanosesquiterpenoids occurring in the volatile essential oil have been shown to have antiseptic and antifungal activities (Alyafei, 2020). This genus is known to have anti-inflammatory, antibacterial, antiseptic, and local anesthetic properties (Latha et al.,
2021). Myrrhterpenes A and B are two cadi­nane sesquiterpenes that are found in the resin of this species and showed potent anti-inflammatory effects by inhibiting NO production (Bao etal., 2021). A mixture of C. myrrha oil with vitamin E acetate showed anti­viral activity in one study (Madia etal., 2021).
Commiphora gileadensis (L.) C. Chr.
Commiphora gileadensis is from the family Burseraceae. Its extract has been used tradition ally
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in Arabic medicine to treat headache. The total extract has shown antiulcerogenic property. The aerial parts were reported to contain tri­terpenes such as oleanonic acid, friedelin, and canophyllal. The ethyl acetate fraction of dry plant material extraction showed antibacterial activity against P. aeruginosa, S. aureus, and me- thicillin-resistant Staphylococcus aureus (MRSA). Quercetin and mearnsetin are the flavonols found in this plant that show antioxidant ac­tivity. Syringic acid is another compound that is related to antimycobacterial and anti­malarial properties (Abbas etal., 2007). The essential oil has also antibacterial and anti­oxidant activity (Al-Massarany etal., 2008).
Cydonia oblonga Mill.
Functional compounds of Cydonia oblonga include steroids, phenolics, terpenoids, fla­vonoids, tannins, organic acids, sugars, and glycosides (Table 8.6). C. oblonga seeds con­tain sterols, tannins, and triterpenes, with a high amount of phenolic compounds such as apigenin, -(–)-quinic acid derivatives, 6-C­pentosyl-8-C-glucosyl chrysoeriol, and stel-
Table 8.6. Major phytochemicals of Cydonia oblonga seeds. (From Ashraf etal., 2016.)
larin, while the major phenolic component of C. oblonga fruit is 5-O-caffeoylquinic acid (Silva etal., 2005).
In another study, the antimicrobial activity of fruit and seed extracts of C. oblonga was evaluated by diffusion agar and microdilution methods. The study showed that the ethanolic extract of C. oblonga seeds had the most effect against K. pneumoniae, Escherichia coli, and En- terobacter aerogenes in comparison with aque­ous ones (Alizadeh etal., 2013). In a study, the antiradical and antioxidant actions of C. oblonga peel, pulp, jam, and seed were evaluated through the 2,2-diphenylpicrylhydrazyl (DPPH) method, showing that the methanolic extract of freeze-dried seeds is the most powerful antioxi­dant in this plant (Silva et al., 2004). A study evaluated the antispasmodic activity of C. oblon- ga in the tracheal tissues of rabbits. Results showed that this action was related to the an­tagonist Ca
2+
activity, which relaxes the trachea in bronchitis and asthma patients; however, this extract can cause mild spasm because of stimulation of the muscarine receptors (Janbaz et al., 2013). An in vitro study evaluated the anti-inflammatory effect of the C. oblonga seed extract on the human cell line THP-1 that was polluted by LPS. Results showed that the ex­tract of the seeds had an antiproliferative activ­ity against renal cancer cells in the 500 μg/ml concentration (Al-Snafi, 2016b).
Compound Components
Mucilages
Phenolics 3-, 4- and 5-O-Caffeoyl quinic
Flavones Isoschaftoside, 5-O-caffeoylquinic
Amino acids L-Aspartic acid, L-asparagine,
Fatty acids Palmitic acid, stearic acid, linoleic
L-Arabinose, aldobionic acids,
D-xylose, 4-O-methyl glucose,
2,3,4-tri-O-methyl-D-xylose,
D-glucose, 2,3-di-O-methyl-D-
xylose, 3-O-methyl-D-xylose
acids, apigenin derivatives, 3,5-dicaffeoyl quinic acid, leucenin-2, 6-C-pentosyl-8-C­glucosyl chrysoeriol, stellarin-2, 6-C-glucosyl-8-C-pentosyl chrysoeriol
acid, caffeoylquinic acids
L-glutamic acid, L-glycine, L-isoleucine, L-valine, L-proline, L-alanine, L-leucine
acid, eicosanoic acid, oleic acid
Cucurbita pepo L.
Cucurbita pepo (pumpkin) belongs to the Cu­curbitaceae family. This plant is a good source
of protein, carbohydrate, minerals, and vita­mins. It has traditionally been used as an antioxidant, anti-inflammatory, and anti­viral. In Chinese Medicine, the seeds are said to be good for the lung (Gutierrez, 2016). Re­garding Iranian traditional use, Avicenna in the Canon of Medicine recommends a mixture of bread-paste and pumpkin for cough. It is mentioned that pumpkin has a role in pre­venting lung cancer and controlling its symp­toms. Containing high levels of vitamin A, it is capable of preventing pulmonary emphy­sema in cigarette smokers (Batool and Dadkhah Tehrani, 2014). In another study, compounds
300 Motahare Nayebzadeh etal.
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cucurbitacin B and cucurbitacin E had anti­proliferative property in lung cancer cells (A549) and lung cancer cell lines (NCI-H460) (Gutierrez, 2016). Seeds and seed oil of C. pepo are a rich source of polyunsaturated fatty acids, mainly palmitic and palmitoleic acid, proteins, phytosterols, tocopherols, ca­rotenoids, and antioxidant vitamins. The phenolic compounds, β- and δ-tocopherol, and polysaccharides are related to the anti­oxidant activity. The extract of leaves and also seed oils have exhibited antibacterial ac­tivity (Ratnam etal., 2017).
Ferula gummosa Boiss.
Ferula gummosa is a plant that has been used as an anti-inflammatory, antiseptic, anti-spasm, and painkiller. The oleoresin of F. gummosa is also used in asthma, earache, and as an expec­torant in chronic bronchitis. New studies showed different properties such as spasmo­lytic, antinociceptive, anti-inflammatory, and antimicrobial properties. The oleoresin contains terpenes and terpenoids, arabinogalactan, and some inorganic substances (Hajifattahi etal.,
2016). The essential oil yield was about 11% in a study and the major compounds of that de­termined by one-dimensional gas chromatog­raphy–mass spectrometry (1D GC–MS) were β- and α-pinene and myrcene (Jalali et al.,
2012). Antibacterial activity of F. gummosa was examined against some Acinetobacter strains. The experiment showed that both the essen­tial oil and oleogum resin had considerable ac­tivity and the alcoholic essential oil had more effect on the strains of Acinetobacter (Afshar etal., 2016).
Ferula persica Willd.
Ferula persica is indigenous to Iran and be­longs to the family Apiaceae. It has been traditionally used as antispasmodic and ex­pectorant (Razavi and Janani, 2015) and in sinusitis (Ahvazi etal., 2012). Chemical con­stituents of Ferula species are sesquiterpenes, sesquiterpene coumarins, sesquiterpene coumarin glycosides, and sulfur-containing compounds. Compounds auraptene and
umbelliprenin found in Ferula species have both anti-inflammatory and cancer chemo­preventive properties. Chloroform extract of F. persica’s root showed antifungal activity related to the compounds persicasulfide A and persicasulfide B. In addition, the couma­rine umbelliprenin at a concentration of 500 μg/ml is responsible for antibacterial activ­ity against Bacillus subtilis, Bacillus cereus, E.
coli, K. pneumoniae, S. typhi, S. aureus, and Staphylococcus epidermidis. It is also capable of inhibiting the growth of Leishmania major (Sattar and Iranshahi, 2017). Another study
showed umbelliprenin to be anti-inflamma­tory and a lipoxygenase inhibitor, so it can be used for treating asthma and chronic obstructive pulmonary disease (COPD) (Iranshahi etal., 2009).
Drimia maritima (L.) Stearn
Drimia maritima bulb contains several phy­tochemicals including phenolic compounds (like pelargonidin 3-monoglucoside and cya­nidin 3-monoglucoside), phytosterols (like β- and γ-sitosterol), cardiac glycosides, and alkaloids, which significantly have several pharmacological effects (Bozorgi et al.,
2017). An in vitro study investigated the cytotoxic and anticancer activity of the methanolic extract of D. maritima bulb in MDA-MB-468 and MCF-7 cells. The results showed that this extract could significantly activate caspase and also increase ROS, Bax/ Bcl-2 ratio, and mRNA expression of CHOP (C/EBP homologous protein), TRIB3 (trib­bles-related protein 3), GADD34 (growth ar­rest and DNA damage-inducible 34), and ATF -4 (activating transcription factor 4) as stress markers (Hamzeloo-Moghadam et al.,
2018). A randomized clinical trial evaluated the anti-asthmatic activity of D. maritima syrup. For this purpose, 10 ml of the syrup was administrated to the 60 patients taking anti-asthmatic medicine for 6 weeks, and then symptoms and spirometry parameters were evaluated. The results showed that this syrup could significantly improve forced ex­piratory volume in the first second (FEV1) (Nejatbakhsh etal., 2017).
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Glycyrrhiza glabra L.
The main compounds of Glycyrrhiza glabra root are triterpene saponins like glycyrrhiz­in, flavonoids like glabridin and isoliquiriti­genin, isoflavonoids, chalcones, mucilage, coumarin-GU-12, phytosterols, and arab­inogalactan protein (Table 8.7) (Sharma etal., 2017).
A study investigated the effect of isoliquiritigenin, as a flavonoid of G. glabra root, on tracheal smooth muscle in vivo and in vitro. To learn the mechanism of tracheal re­laxation, the researchers experimented with isoliquiritigenin in guinea-pig tracheal smooth muscle cells (TSMCs) pretreated by acetylcho­line, potassium chloride (KCl), and histamine. It was found that this compound could relax the trachea by increasing cyclic guanosine monophosphate (cGMP) and inhibiting cG­MP-specific phosphodiesterase type 5 (PDE5); also, isoliquiritigenin significantly increased the latency time of collapse and inhibited the lung overflow induced by histamine and acetylcholine (Liu et al., 2008). In an in vivo study, the activity of G. glabra extract on the cellular and humoral immune activation and nonspecific resistance was evaluated in 90 CBA/CaLac mice. The results showed that G. glabra root extract enhanced the cellular
Table 8.7. Major phytochemicals of Glycyrrhiza glabra roots. (From Liu etal., 2008; Ng etal., 2013.)
immune response, and this efficacy was higher than for Echinacea purpurea (Borsuk etal., 2011). In another study, the antitussive effect of an aqueous extract of G. glabra was evaluated in 24 guinea pigs in comparison with codeine, showing that the polymeric fraction of G. glabra decreased the amount of citric acid in the animals, which is the major cause of cough (Saha etal., 2011).
The anti-inflammatory effect of glabri­din was evaluated in an in vivo study through inducing inflammation and airway hyperres­ponsiveness in BALB/c mice by intraperito­neal ovalbumin and aluminum hydroxide (Al(OH) that glabridin at a dose of 20–30 mg/kg sig-
) administration. The study showed
3
nificantly decreased immunoglobulin (Ig)E level, leukoctye count, and total protein, so it can be effective in asthma treatment (Dogan et al., 2020). The antitussive activity of the ethanol extract of G. glabra roots and rhi­zomes was investigated in 36 albino mice with cough induced by sulfur dioxide (SO2) gas. The results showed that this extract, in comparison with codeine sulfate, could sig­nificantly inhibit up to 35.62% of coughs in 60 min (Jahan and Siddiqui, 2012). The anti-inflammatory effect of glycyrrhizin, as a saponin compound in G. glabra, was evalu­ated in 36 BALB/c mice with acute lung injury induced by LPS to assay its mechanism; it was shown that glycyrrhizin inhibited the toll-like receptor-4 (TLR-4)/NF-κB pathway and pro­tected the lung tissue (Lee etal., 2019).
Compound Components
Flavonoids Glabridin, isoliquiritigenin,
Phenolics Isoangustone A,
Volatile
components
liquiritin, rhamnoliquirilin, liquiritigenin, prenyllicoflavone A, glucoliquiritin apioside, 1-methoxyphaseolin, shinpterocarpin, shinflavanone, licopyranocoumarin, glisoflavone, licoarylcoumarin
semilicoisoflavone B, licoriphenone, 1-methoxyficifolinol
Pentanol, tetramethyl pyrazine,
hexanol, terpinen-4-ol, linalool oxide A, linalool oxide B, geraniol, α-terpineol
Hyssopus officinalis L.
Hyssopus officinalis contains several compounds such as flavonoids (like quercetin and apigenin­7-glucoside), polyphenols (like gallic acid), vola­tile oil, tannins, terpenoids, and murrain. The important compounds of hyssop essential oil are pinocamphone, pinocarvone, β-pinene, ter­pinene-4-ol, isopinocamphone, p-cymene, myr­tenal, and carvacrole. The phenolic compounds of the alcoholic extract of hyssop comprise caf­feic acid, kaempferol, apigenin, cinnamic acid, naringenin, and cateachin (Süleyman et al., 2010; Karegar-Borzi etal., 2016; Abdel-Megeed et al., 2020). An in vitro study examined the antioxidant and antimicrobial effects of hyssop
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essential oil. To evaluate the antimicrobial activ­ity of this oil, the disk diffusion test was done for E. coli, P. aeruginosa, S. aureus, and Staphylo- coccus pyogenes, showing that 5–10 μl of the oil can inhibit the E. coli, S. aureus, and S. pyogenes. For assaying the antioxidant activity of this oil, in comparison with acetic acid and butylated hydroxytoluene (BHT), the DPPH method was used, showing that hyssop oil has lower antioxi­dant action in comparison with BHT and acetic acid (Süleyman etal., 2010). In an in vivo study, the anti-remodeling and anti-inflammatory ef
­fects of the aqueous extract of hyssop were evaluated. Asthma was induced in 32 BALB/c mice by Al(OH) cacy of this extract in comparison with dexa-
and ovalbumin; then, the effi-
3
methasone was evaluated. The results showed that hyssop extract decreased the expression of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) by collagen deposition, proliferation of smooth muscle, and mucus secretion (Ma etal., 2014a). Thirty-two BALB/c mice were investigated to determine the effect of aqueous extract of hys­sop on asthmatic condition in comparison with dexamethasone; it was concluded that hyssop extract decreased the level of IgG and increased the ratio of eosinophils (EOS). These results showed that this extract, via modulating the immune system, had a positive effect on asthma management (Ma etal., 2014b). A ran­domized clinical study investigated the anti­asthmatic action of a mixed herbal mixture containing Matricaria chamomilla, A. capillus-
veneris, H. officinalis, G. glabra, A. officinalis, and Malva sylvestris on 46 children suffering from
asthma. The patients took this herbal mixture from the first day of starting signs to five days. The results showed that this herbal mixture significantly reduced the nighttime awakening and severity of cough, whereas it did not im­prove tachypnea, wheezing, and respiratory distress (Javid etal., 2019).
(Alamgeer etal., 2018). In Iran, it has been used traditionally to treat respiratory dis­orders with sticky and thick secretions. It contains minerals, vitamins, fat, protein, phenolic, trypsin inhibitor, linatine, lignans (phytoestrogens), and Se. These compounds are shown to have roles in affecting cystic fi­brosis pulmonary pathogenesis (Tahermo­hammadi etal., 2021). The seeds are a rich source of α-linolenic acid (ALA; C18 : 3n-3) and linoleic acid (LA; C18 : 2n-6), which are essential fatty acids. n-3 Fatty acids can help prevent some inflammatory diseases. L. usi- tatissimum is a rich source of lignan that seems to have antioxidant property depending on the presence of specific bacteria. This plant also contains soluble and insoluble fibers. Mucilage is the most soluble fiber existing in L. usitatissi- mum (Jhala and Hall, 2010).
Liquidambar orientalis Mill.
Liquidambar orientalis, known as Asian storax, is produced when the bark of sweetgum trees is damaged. It has been used for a long time to cure cough, skin problems, and wounds. Major components of L. orientalis are cinnam­ic derivatives, vanillin, and styrene. Cinnamic acid presents antibacterial and antioxidant activities. Oxygenated monoterpenes and monoterpene ketone groups also account for considerable antioxidant activity. The sap also possesses antifungal and immunosuppres­sant properties (Lingbeck et al., 2015). The wound healing property was tested on young Yorkshire pigs with excised wounds on their back; the results showed that wound healing was related to cinnamic acid and esters such as cinnamyl cinnamate and storesinol that help the proliferation phase to be potent and increase both granulation and re-epitheliali­zation (Ocsel etal., 2012).
Linum usitatissimum L.
Linum usitatissimum (flax or linseed) from family Linacaea has been used as a natural laxative for many years. The seed, bark, leaves, flower, and oil of this plant have traditionally been used for cough and asthma in Pakistan
Malva sylvestris L.
Malva sylvestris contains various phytochem­icals with several pharmacologic activities; these compounds include flavonols, tannins,
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mucilage, polyphenols, flavonoids, and folic acid (Irfan etal., 2021). The antimicrobial activ­ity of the hydroalcoholic extract of M. sylves- tris was evaluated in an in vitro study by using disk diffusion and microdilution methods against Aggregatibacter actinomycetemcomi- tans. The result showed that M. sylvestris, with minimum inhibitory concentration of 156.2 μg/ml, had an antimicrobial activity against periodontal diseases (Vahabi etal., 2019). An in silico study evaluated the potential of the methanolic extract of M. sylvestris in the treatment of COVID-19 by acting on the 6LU7 viral protein. On the other hand, the in vitro examination of the antioxidant effect of this plant was evaluated by DPPH and NO bioassay. The results showed that this plant extract was significantly effective in the treatment of SARS-CoV-2 resistance (Irfan etal., 2021).
Myrtus communis L.
Myrtus communis has several important sec­ondary metabolites such as tannins, flavon­oids, and essential oils. Studies showed that M. communis fruit contains 14 fatty acids, its major ones being oleic acid, palmitic acid, and stearic acid. Additionally, the pharmaco­logic effect of M. communis fruit essential oil is important because of the existence of 1,8-cineole, α-terpineol, and α-pinene (Serce etal., 2010; Kutlu et al., 2021). An in vitro study was conducted on the anti­inflammatory action of M. communis fruit through inducing endotoxemia in human umbilical vein endothelial cells (HUVECs) by LPS administration. The results showed that the 1,8-cineole and α-pinene of M. communis significantly reduced the expression of in­flammation markers such as IL-1β, TNF-α, endothelial nitric oxide synthase (eNOS), and IL-6 (Kutlu et al., 2021). The antioxi­dant capacity of the methanol extract of M. communis fruit was evaluated by DPPH and β-carotene/LA; the study showed that this extract was a good antioxidant through scavenging free radicals and inhibiting lipid peroxidation (Serce etal., 2010). An in vivo study compared the effect of black and white M. communis fruit and leaves on hepatic
ischemia-induced rats. For this purpose, the researchers used the leaves and fruit extract 15 min before reperfusion and then evalu­ated the metabolism capacity of the liver. The concentration of total phenols (TP) in these extracts was different; the TP of white fruit and black leaves (27 and 94.3 μg/ml, re­spectively) showed more effectiveness. The extract of white fruit showed a reduction in the markers aspartate aminotransferase (AST), malondialdehyde (MDA), and alanine aminotransferase (ALT), and an increase in the concentration of monoethylglycinexyli
­dide (MEGX) (Ferchichi, 2012). An open-la­bel randomized clinical trial investigated the efficacy of M. communis fruit syrup in 18– 65-year-old outpatients with mild to moder­ate COVID-19; now, this trial is in phase three of evaluation (Azimi and Hashemi­nasab, 2020).
Nymphaea alba L.
Nymphaea alba has a high content of several phytochemicals including flavonoids (quer­cetin), tannins, tocopheryl esters, phenolic acids, kaempferol, apigenin, and isokaemp­feride. Particularly, N. alba conains ellagic acid and gallic acid such as p-hydroxybenzo- ic, ferulic, and vanillic acids as methyl and ethyl esters of them. Among these com­pounds, the major compounds of N. alba are quercetin, apigenin, and ellagic acid (Cudal­beanu etal., 2018). The antiviral activity of the methanolic and acetonic extracts of N. alba was evaluated in vitro, which was used to examine the anti-hepatitis C virus (HCV) effect of these extracts in the Huh-7 cell line. The result showed that N. alba flower extract was significantly effective in the treatment of HCV with or without another anti-HCV drug (Rehman et al., 2018). The anticarcinogenic activity of methanolic ex­tract of N. alba flowers was evaluated in Wis­tar rats with renal oxidative trauma induced by iron nitrilotriacetate (Fe-NTA) adminis­tration. Results showed that administration of the plant extract at 100–200 mg/kg dose significantly decreased γ-glutamyl transpeptida se, xanthine oxidase, lipid peroxidation, and
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hydrogen peroxide (H2O2) generation, which also recovered the normal level of antioxi­dant enzymes and glutathione-metabolizing enzymes (Khan and Sultana, 2005).
Opopanax chironius (L.) W.D.J. Koch
Opopanax chironius is a plant from the family Apiaceae with deobstruent, antispasmodic,
antipyretic, and expectorant activity that has also been used in asthma (Maggio etal., 2013; Önder etal., 2020). This plant is rich in cou­marins, especially furanocoumarins and sim­ple prenylated coumarins. Phthalides are an­other phytochemical observed in O. chironius. Gum and malic acid are active components for treating asthma. Imperatorin and heraclenin are the compounds related to the anticancer activity of this plant that induces apoptosis in Jurkat leukemia cells (Önder etal., 2020).
Papaver somniferum L.
Papaver somniferum, with the common name poppy, belongs to the family Papaveraceae. More than 40 alkaloids exist in this plant in­cluding morphine, codeine, thebaine, and noscapine as the most important ones. Avi­cenna ( 980–1037) introduced poppy as the most powerful analgesic. Morphine reduces the sensation of pain and suppresses the cough reflex. Codeine is also a very important antitussive and is used in many antitussive products. Other compounds such as ethyl morphine, phal codeine, hydrocodone, and oxycodone also have antitussive properties (Yazdani etal., 2003). The seeds and fruits of P. somniferum have been used for cough and the seeds have also been used in Unani Medi­cine to treat asthma as well (Masihuddin etal.,
2018). In Pakistan, seeds and fruit have been used as antitussives (Alamgeer etal., 2018).
proteins, and carbohydrates were found to be relatively abundant. Also, the oil yield on a dry weight basis was observed to be 49.45% (Tha­kur, 2015). The kernel and the oil obtained from P. gerardiana are a rich source of fatty acids, especially unsaturated fatty acids like LA (n-6) and oleic acid (n-9) that have many health benefits (Cai etal., 2013; Sheikhahmadi etal.,
2020). γ-Tocopherol and α-tocopherol are the most abundant tocopherols in the oil (Sheikhahmadi etal., 2020). Albumenoids, oil starch, phytosterol, polyphenols, xanthenes, carotenoids, tocopherols, catechin, etc. are also found in P. gerardiana nut. According to the Ayurvedic Pharmacopoeia, this plant is used in the treatment of cough and asthma (Singh etal., 2021).
Pistacia terebinthus L.
Pistacia terebinthus that belongs to the fam­ily Anacardiaceae is commonly known as terebinth. Smoke of the resin has been used as an air purifier and antiseptic in Iran. In Greece, it has been considered an expector­ant. The fruit in Turkey is known as an anti­tussive, stimulant, and for cold and flu treat­ment, while the resin has traditional uses with anti-inflammatory, antipyretic, and re­spiratory antiseptic effects and was con­sidered to be good for asthma. The major compounds in the essential oil of P. terebin- thus are hydrocarbon and oxygenated mono­terpenes such as α-pinene, and the resin commonly contains triterpenes. Masticadi­enonic acid, masticadienolic acid, and morolic acid are compounds with anti-inflammatory effect. Flavonoids, fatty acids like oleic acid, and sterols such as β-sitosterol are also reported in the fruits of P. terebinthus (Bozorgi etal., 2013).
Pistacia vera L.
Pinus gerardiana Wall. ex D. Don
Pinus gerardiana, also known as chilgoza, is considered to have carminative, stimulant, and expectorant activity. In a study, the oils,
Known as pistachio, Pistacia vera is a nut from the Anacardiaceae family. P. v e r a is an excellent source of unsaturated fatty acids, antioxidants, dietary fibers, proteins, and minerals (Kashaninejad and Tabil, 2011).
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P. v e ra kernels contain 50 to 60% fat which mostly includes linoleic, linolenic, and oleic acids (Kashaninejad etal., 2006). In Iran, it was used traditionally as a food and in Tur­key, the resin was used for treating asthma. New researches show that anti-inflamma­tory and antimicrobial properties are related to different terpenoids. Also, antioxidant ef­fects are associated with high levels of fla­vonoids and phenols (Bozorgi etal., 2013). Regarding the anti-inflammatory effect, an experiment showed that a polyphenols-rich extract of natural raw shelled pistachio considerably reduced the paw edema and neutrophilic infiltration in rats. It is also believed that epicatechin and isoquercetin concentrations are responsible for antioxi
-
dant and anti-inflammatory properties. A significant reduction in TNF-α and IL-1β levels was observed following consumption of natural raw shelled and roasted salted pistachios (Paterniti etal., 2017).
Plantago ovata Forssk.
Plantago ovata seeds have several compounds in the outer coat including mucilage, and com­pounds in the neutral and acidic polysacchar­ides fractions from mucilage are -galactose, -arabinose, -rhamnose, -galacturonic acid, and -xylose. Gallic acid and rutin are the main polyphenol compounds of P. ov at a seeds (Talu­kder etal., 2016; Sarfraz etal., 2017). The anti­bacterial and anti-inflammatory action of the aqueous extract of the leaves and seed of P. ovata was evaluated. For this purpose, the anti­bacterial activity of these extracts was evaluated by the tube dilution method against peri­odontal pathogens including Porphyromonas
gingivalis, A. actinomycetemcomitans, Fuso­bacterium nucleatum, and Prevotella intermedia.
On the other hand, the anti-inflammatory effect of P. o v a t a aqueous extract was investi­gated by zymogen gel electrography against MMP-2 and MMP-9. The results showed that these extracts were effective in inflammatory and bacterial infection of periodontal diseases (Reddy eta l., 2018). An in vivo study in HL A-B27 rats evaluated the anti-inflammatory effect of psyllium in the intestinal inflammatory
pathway and its intermediates, which showed that this plant seed decreased the leukotriene B4, NO, and TNF-α in inflammatory processes (Sarfraz etal., 2017).
Prunus dulcis (Mill.) D.A. Webb
Almond (Prunus dulcis) is a good source of vita- min E, magnesium, manganese, copper, phos­phorus, fiber, riboflavin, as well as phenolic and polyphenolic compounds. Studies show that the kernels are rich in monounsaturated fatty acids (MUFAs), which are known to be beneficial, especially for the cardiovascular system. The oil contains high amounts of oleic acid as the major fatty acid, and other com­pounds such as sterols, tocopherols, and squa­lene (Čolić etal., 2019). As to treatment, it is suggested that the paste of soaked almond with butter helps to relieve cough (Sultana etal., 2016). The anti-inflammatory property of almond was investigated in a randomized, single-blind, crossover, controlled feeding study. The group receiving a high-almond diet had lower levels of E-selectin than the control and low-almond groups. Both groups with almond diets showed a decrease in the serum level of C-reactive protein (CRP). MUFAs seem to be responsible for the decrease in CRP and E-sele ctio n levels and, as a result, for the anti-inflamma­tory effect (Rajaram et al., 2010). Another study shows the role of P. dulcis as the core drug in treating exogenous cough and acute bronchitis. The mechanism may involve ara­chidonic acid metabolism, peroxidase, estro­gen metabolism, and tryptophan metabolism pathways (Sun etal., 2020).
Viola odorata L.
Viola odorata contains several compounds including alkaloids (like the emetocathartic alkaloid violine), saponins, glycosides, tan­nins, mucilage, coumarin, methyl salicylate, monoterpenes and sesquiterpene terpenoids (like phenyl butanone, phenyl butanone, and viridiflorol), vitamin C, and flavonoids (like gallic acid and quercetin). Additionally, the essential oil of V. odorata includes geraniol,