{"id":56735,"date":"2024-03-20T11:56:19","date_gmt":"2024-03-20T11:56:19","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=56735"},"modified":"2024-04-01T18:53:58","modified_gmt":"2024-04-01T18:53:58","slug":"a-summary-of-the-pharmacological-activity-phytochemistry-and-pharmacognosy-of-parthenocissus-quinquefolia-l-review-article","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no1\/a-summary-of-the-pharmacological-activity-phytochemistry-and-pharmacognosy-of-parthenocissus-quinquefolia-l-review-article\/","title":{"rendered":"A Summary of the Pharmacological Activity, Phytochemistry, and Pharmacognosy of Parthenocissus quinquefolia (L.): Review Article"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Parthenocissus\nquinquefolia (L.)<\/em> is a significant member of the Vitaceae family of medicinal herbs.\nDue to their reputation as the origin of wine, raisin, and grape cultivation,\nthis family is highly significant economically 1<\/sup>. Additionally, this\nfamily is well-known for its pharmacological activity, which includes its\nability to prevent cancer 2<\/sup>, relieve sore throats, treat rheumatism,\narthritis, gastrointestinal tract issues, heal fractures, protect bone coming\nfrom postmenopausal bone loss, and have anti-parasitic, anti-diabetic,\nanti-dysentery, anti-diarrhea, diuretic, anti-inflammatory, anti-convulsant,\nanxiolytic, and anti-cholesterol formation activity 3<\/sup>.<\/p>\n\n\n\n

Of\nthe approximately twelve species of the Parthenocissus<\/em> genus, nine are in\nAsia, three are in North America, and just one is in Central America and the\nCaribbean 4<\/sup>. Greek terms parthenos (meaning “virgin”) and\nkissos (meaning “ivy,” which was Latinized to form Cissus) are the\nsources of the Parthenocissus<\/em> name. This naming is related to the\nability of these creepers to form seeds without pollination 5<\/sup>. Most\nof this genus plants are used as ornamental creepers for decorative\nrequirements, as they appear most obviously in the spring with their new bright\ngreen leaves. At the same time, in the autumn, they shine in dramatic changes\nin leaf color that may vary from yellow, orange-brown, and red to violet 6<\/sup>.\nIt has become naturalized in southern Africa, Australia, tropical and temperate\nAsia, and Europe. Although P. quinquefolia<\/em> is widely recognized to grow\nin household gardens from north to south and to germinate in numerous plant\nhouses, its distribution in Iraq has yet to be formally documented 7<\/sup>.\n<\/p>\n\n\n\n

Taxonomic classification<\/strong><\/strong><\/p>\n\n\n\n

Plantae or plant is the Kingdom, Viridiplantae is the Subkingdom,\nStreptophyta is the Infrakingdom, Embryophyta is the Superphylum, Tracheophyta\nis the Phylum, and Spermatophytina is the Subphylum. <\/p>\n\n\n\n

Magnoliopsida is the class; Rosanae is the superorder;\nVitales is the order; Vitaceae is the family; Parthenocissus Planch<\/em> is the\ngenus; and Parthenocissus quinquefolia<\/em> is the species8, 9<\/sup>.<\/em><\/p>\n\n\n\n

Common\nnames of Parthenocissus quinquefolia<\/em><\/strong><\/p>\n\n\n\n

Parthenocissus quinquefolia<\/em> is also called woodbine, Virginia creeper,\nAmerican ivy, and five-leaved ivy. In Iraq, it’s known as MAKHALEB AL-KETT 7<\/sup>.\nThe plant synonyms are Ampelopsis hederacea<\/em>, Ampelopsis quinquefolia<\/em>,\nand Hedera quinquefolia<\/em> L. 8, 9<\/sup>.<\/p>\n\n\n\n

Plant description<\/strong><\/p>\n\n\n\n

Quinquefolia<\/em> is derived from the Greek word meaning\n“five leaves.” Quinque signifies five, whereas folia refers to leaves\nor foliage 10<\/sup>.<\/p>\n\n\n\n

Parthenocissus\nquinquefolia<\/em> (Fig. 1) shows climbing characteristics that\nmay reach up to 30 meters in height; its five leaflet leaves, which have\nenlarged or jointed nodes, emerge sporadically on shoots. These may produce\nlittle, forked tendrils with flower clusters; the greenish clusters develop in\nlate spring and ripen into small, hard, purplish-black berries in early fall,\nopposing the leaves. The tendrils are capped with small, intensely sticky pads.\nThe stamens develop opposing the petals, and most of the tiny flowers’\ncomponents appear in groups of four or five 11<\/sup>.<\/p>\n\n\n\n\n\n
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Figure 1:<\/strong> Parthenocissus quinquefolia<\/em>. A- Climbing feature at the Iraqi gardens. <\/strong>B-<\/strong> Red-colored leaves and berry clusters.<\/strong><\/p>\n

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Traditional uses of Parthenocissus quinquefolia<\/em><\/strong><\/p>\n\n\n\n

The bark\nand fresh young stem are traditionally used to relieve constipation, besides\ntheir usage as emetic, expectorant, and tonic 12<\/sup>. A soft and moist\nmaterial prepared by a hot plant decoction can be applied to the body to reduce\nedema 13<\/sup>. While a tea prepared from the plant is used to treat\njaundice, a tea prepared from the roots is used to treat diarrhea and\ngonorrhea. A tea made from the leaves is an astringent, aperient, and diuretic 13,\n14<\/sup>. Fruit aids with fever treatment 15<\/sup>. Also, the plant was\nused as a natural source of pink dye obtained from the fruit 13<\/sup>. As\nan Ayurvedic ethno-medicinal plant, P. quinquefolia<\/em> is used as an\nantihyperglycemic agent by the Indian population 16<\/sup>.<\/p>\n\n\n\n

Native\nAmericans (Cherokee people) have a rich ethnobotanical heritage; they prepared P.\nquinquefolia<\/em> as an infusion for jaundice 17<\/sup>. Parthenocissus\nquinquefolia<\/em> berries are rich in oxalic acid, and this gives the\nexpectation of being poisonous upon eating 18<\/sup>. Since the plant was indigenous to Central\nand North America, most of the traditional uses were in the different tribes of\nthe Native Americans, which are summarized in tab.1.<\/p>\n\n\n\n

Table 1: Traditional uses of Parthenocissus quinquefolia<\/em> in populations\/Tribes.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
\n

Traditional uses<\/strong><\/p>\n<\/td>\n

\n

Different populations\/Tribes<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Infusion used for jaundice.<\/p>\n<\/td>\n

\n

Native American \/The Cherokee and Iroquois.<\/p>\n<\/td>\n<\/tr>\n

\n

Herbal remedy for diarrhea, swelling, and as a urinary aid.<\/p>\n<\/td>\n

\n

Native American \/The Cherokee and Iroquois.<\/p>\n<\/td>\n<\/tr>\n

\n

Decoction of the root for diarrhea treatment.<\/p>\n<\/td>\n

\n

Native American \/Mesquakie.<\/p>\n<\/td>\n<\/tr>\n

\n

Pink dye from the fruit for the skin<\/p>\n<\/td>\n

\n

Northern American Indian \/Kiowa.<\/p>\n<\/td>\n<\/tr>\n

\n

Antihyperglycemic agent.<\/p>\n<\/td>\n

\n

 Indian population.<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Phytochemical\nconstituents of Parthenocissus quinquefolia<\/em><\/strong><\/p>\n\n\n\n

Phytochemical\ninvestigation performed on the bark, stem, leaves, and fruit extracts of P.\nquinquefolia<\/em> indicated the presence of significant secondary metabolites,\nincluding terpenoids, alkaloids, saponins, steroids, polyphenolic compounds (flavonoids,\nphenolic acids, and tannins), anthraquinones, cardiac glucosides, coumarins,\nand reducing sugars. The essential secondary metabolites identified and\nisolated from P. quinquefolia<\/em> include stilbenes, polyphenolic compounds,\nterpenes 7<\/sup>, fatty acids, and others 19-21<\/sup>.<\/p>\n\n\n\n

Stilbenes compounds<\/strong><\/p>\n\n\n\n

The name\n“stilbenes” comes from the Greek word “stilbos,” which\nmeans “shining”; these plants exhibit fluorescence 22<\/sup>.\nStilbenes are phytoalexins that plants create as a defense mechanism or a means\nof fending off illness when they are harmed, stressed, or exposed to other\nenvironmental factors. Stilbenes exist in two stereoisomer configurations: the\ncrowdy Cis (Z) isomer and the relieved Trans (E) isomer, and have a skeleton\ncomposed of C6-C2-C6 carbon atoms 23<\/sup>. Many types of stilbenes were\ndetected and isolated from P. quinquefolia, <\/em>including two monomeric\nstilbenes (trans-resveratrol, piceatannol), one glycoside stilbene (resveratrol\n2-O-\u03b2- glucopyranoside), two resveratrol oligomer (parthenocissins A, B), three\nresveratrol dimers (resveratrol trans-dehydrodimer named \u0263-viniferin, \u03f5-viniferin,\nand pallidol), one oligostilbene (parthenocissins N), two oligostilbene\nresveratrol dimer (cyphostemmin A, cyphostemmin B), and one resveratrol trimer\n(Miyabenol C)24-26<\/sup>. Some Stilbenes compounds’ chemical structures of\nP. quinquefolia <\/em>have been demonstrated in Fig.2.<\/p>\n\n\n\n\n\n
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Figure 2:<\/strong> Some Stilbenes compounds’ chemical structures of Parthenocissus quinquefolia <\/em>27-29<\/sup>.<\/strong><\/p>\n

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Polyphenolic compounds<\/strong><\/p>\n\n\n\n

A- Flavonoids are essential secondary metabolites extracted from\ndifferent medicinal plants and known for their use in nutraceutical,\npharmaceutical, therapeutic, and cosmetic applications 30<\/sup>. In terms\nof chemistry, flavonoids are composed of a 15-carbon skeleton that is arranged\nin the C6-C3-C6 structure, in which both of the C6 are benzene rings named A\nand B, while the C3 acts as a bridge link between the A and B rings. This later\nbridge can again be cyclized by oxygen and produce a new ring called the C ring\n(oxygen-containing pyrene ring31<\/sup>).<\/p>\n\n\n\n

This compound’s ability to modify important cellular enzyme\nactivities results in several health advantages, including anti-inflammatory,\nanti-mutagenic, anti-carcinogenic, and antioxidant properties. Furthermore,\nflavonoids are valuable against many diseases, including cancer, Alzheimer’s,\natherosclerosis, and others. This is due to their potent inhibition of numerous\nenzymes like phosphoinositide 3 kinase, cyclo-oxygenase, xanthine\noxidase, and lipoxygenase30, 32<\/sup>. Numerous flavonoids, including quercetine-3O-\u03b1-L-rhamnoside,\nmyricetine-3-O-\u03b1-L-rhamnoside, quercitrin (quercetin O-glycoside), and rutin\n(quercetin 3-O-rutinoside), have been found as glycosides (Fig. 3) 24<\/sup>.\nOn the other hand, flavonoids can exist as free aglycones (Fig. 4), like quercetin,\nkaempferol, isorhamnetin, and luteolin 7<\/sup>.<\/p>\n\n\n\n\n\n
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Figure 3:<\/strong> Flavonoid chemical structures as glycosides <\/strong>of Parthenocissus quinquefolia<\/em> 33, 34<\/sup>.<\/strong><\/p>\n

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Figure 4:<\/strong> Flavonoid chemical structures as an aglycone of Parthenocissus quinquefolia<\/em> 34, 35<\/sup>.<\/strong><\/p>\n

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Also,\nother types of flavonoids, which are anthocyanins(Fig. 5), were isolated and\nidentified from the fruit (berries) of P. quinquefolia<\/em> and considered\nnatural colorants like delphinidin (blue pigment), petunidin (dark-red or\npurple pigment), cyaniding (reddish-purple pigment), malvidin (reddish blue\npigment), peonidin (purplish-red pigment), and pelargonidin (orang pigment)36<\/sup>.<\/p>\n\n\n\n\n\n
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Figure 5: <\/strong>Anthocyanins visible pigmentation rang 37<\/sup>.<\/strong><\/p>\n

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B- Phenolic acids are one of the simple and essential\nsecondary metabolites with phenol units in their structure 38<\/sup>. Some essential\nphenolic acids (Fig. 6) have been demonstrated in the whole plant of P.\nquinquefolia, <\/em>like coumaric acid, caffeic acid, and chlorogenic acid, which\nis derived from cinnamic acid. It also contains gallic acid, a benzoic acid\nderivative 39, 7<\/sup>.<\/p>\n\n\n\n\n\n
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Figure 6:<\/strong> Phenolic acid compounds’ chemical structures of Parthenocissus quinquefolia <\/em>40, 34<\/sup>.<\/strong><\/p>\n

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Terpenes and Terpenoids<\/strong><\/p>\n\n\n\n

Among phytochemicals, triterpenes are the most representative\nclass, with approximately 30,000 known constituents representing a portion of\nall plants’ lipid substances 41<\/sup>. Only one triterpenic compound was\nidentified from P. quinquefolia,<\/em> which is \u03b2- Amyrine\n(\u03b2-Amyrylhexadecanoate hexadecanoate), and its structure is shown in Fig. 7.\nThis compound was extracted from dried leaves using dichloromethane for 24 h in\na Soxhlet apparatus, then eluted with a mixture of solvents of increasing polarity\nusing column chromatography and evaluated for antithrombotic effect 42<\/sup>.<\/p>\n\n\n\n\n\n
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Figure 7:<\/strong> \u03b2- Amyrin chemical structure isolated from Parthenocissus quinquefolia<\/em>.<\/strong><\/p>\n

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B- Phytosterols\nare cholesterol-like molecules found in higher plants 43<\/sup>. Upon TLC\nand HPLC examination of the petroleum ether fraction of the whole plant\ndemonstrated the presence of stigmasterol and beta-sitosterol, and the\nquantities of both compounds in the petroleum ether fraction were calculated\nand found to be 2.33 \u03bcg for stigmasterol and 4.4 \u03bcg for beta-sitosterol 7<\/sup>.<\/p>\n\n\n\n

Fatty acids<\/strong><\/p>\n\n\n\n

Aliphatic\nmonocarboxylic acids are known as fatty acids and typically consist of a 4\u201328\ncarbon chain that is even-numbered, unbranched, and perhaps saturated or\nunsaturated 44, 45<\/sup>. Plants synthesize a wide variety of fatty acids,\nalthough only a few are major and standard constituents46<\/sup>. So, the\nmost abundant and significant fatty acids of P. quinquefolia <\/em>seeds were\npalmitic, oleic, and linoleic acids, which evaluated the plant’s seed extract for\nantioxidant capacity. 20, 47<\/sup>. The most abundant and significant\nfatty acids of P. quinquefolia <\/em>are demonstrated in Fig. 8.<\/p>\n\n\n\n\n\n
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Figure 8:<\/strong> Chemical structure of the most abundant and significant fatty acids of P. quinquefolia <\/em>48<\/sup>.<\/strong><\/p>\n

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Others<\/strong><\/p>\n\n\n\n

Other constituents of P. quinquefolia<\/em> have been\nreported, including tropane alkaloid in glycosidic form, which was isolated\nfrom the chloroform fraction of the whole plant, and the proposed structure has\nbeen identified using liquid chromatography-mass spectrometry and Fourier\ntransform infrared analysis. Butanol fraction of the whole plant could contain\nsennoside C, Asiatic acid or its analogue, Madecassic acid, and triglyceride 1,\n2-dipalmitoyl-3-oleoyl-glycerol, which were identified based on the NIST library\nand multiple analytical tests7<\/sup>.<\/p>\n\n\n\n

Pharmacological activity of Parthenocissus quinquefolia<\/em><\/strong><\/p>\n\n\n\n

Antidiabetic activity<\/strong><\/p>\n\n\n\n

Diabetes\nmellitus (DM), is a chronic metabolic illness, a significant global health\nissue, and one of the leading causes of morbidity in the world, with a\nsignificant burden in developing countries 16,49<\/sup>. The number of\npeople with diabetes was 171 million in 2000; by 2030, it is predicted to reach\n366 million 50, 51<\/sup>.<\/p>\n\n\n\n

Exercise\nand diet are crucial for managing hyperglycemia, yet 90% of patients with type\n2 diabetes struggle to maintain long-term glucose control and need\nantihyperglycemic medications to achieve this 52<\/sup>.<\/p>\n\n\n\n

An\nIndian Ayurvedic herb was tested for its antidiabetic properties in a Zucker\ndiabetic rat model using blood insulin levels and an oral glucose tolerance\ntest. To ascertain the plant’s mode of action, 250 mg\/kg body weight of\nlyophilized 70% ethanolic extract was used. Consequently, a potent antidiabetic\nimpact was observed, wherein blood glucose levels decreased in direct\nproportion to insulin levels. This suggests that P. quinquefolia<\/em>\ncontributes to improving insulin release53<\/sup>. <\/p>\n\n\n\n

Anti-inflammatory activity<\/strong><\/p>\n\n\n\n

Inflammation\nis a body response and physiological defense mechanism against foreign invaders\nor exposure to tissue injury, oxidative stress, or pre-existing disease 54,\n55<\/sup>. Inflammation is of two types, acute and chronic, in which the\naccumulation of plasma proteins in tissues occurs, leading to increased fluid\nperfusion that results in swelling. This is followed by leukocyte release,\nwhich moves toward the affected area and subsequently releases cytokines, which\nare pro-inflammatory mediators and cause immune cell activation 56-58<\/sup>.\nThese cytokines include tumor necrosis factor-alpha and different types of\ninterleukins (IL-1, 6, 8, and 10) 47,59<\/sup>.  <\/p>\n\n\n\n

Three\ngroups of six albino rats of each gender, weighing between 150 and 170 g, were\nused to affirm the anti-inflammatory properties of P. quinquefolia<\/em>. The\nfirst group received a vehicle, which is dimethyl sulfoxide, and was designed\nas a positive control. The second group received oral treatment with an\nn-hexane fraction of P. quinquefolia<\/em> (250 mg\/kg 53<\/sup>) by\ngastric gavage for seven consecutive days. Ten milligrams of diclofenac\nsodium were administered to the third group 60<\/sup>. This group is used\nas an indicator to determine the level of anti-inflammatory activity.<\/p>\n\n\n\n

The\nplant’s n-hexane fraction, which was analyzed using the GC\/Mass technique,\nrevealed that it contains unsaturated fatty acids, mainly oleic and palmitoleic\nacid. Through nuclear factor suppression, these fatty acids block the\nexpression of pro-inflammatory cytokines such TNF\u03b1 and IL-6, which contribute\nsignificantly to their reduction. DNA transcription, cytokine synthesis, and\ncell proliferation are all facilitated by the protein complex known as\nkappa-light-chain enhancer of activated B cell (NF)-\u03baB signaling. When NF-kB\ntranslocates into the nucleus, two genes associated to inflammation, TNF-\u03b1 and\nIL-6, are elevated 61, 62<\/sup>.<\/p>\n\n\n\n

Furthermore,\nin the visceral adipose tissue, they inhibit NF-\u03baB activation and diminish\nmessenger ribonucleic acid mRNA expression for IL6 and TNF-\u03b1. Also, Siritin-1\n(SIRT-1) is an enzyme in the cell nucleus and has a regulatory role in the cell\n63<\/sup>. Similarly, polyphenols block the development of COX-2 enzymes,\nwhich convert arachidonic acid to prostaglandin, which is involved in swelling,\ndiscomfort, and redness and is released during inflammation 64<\/sup>.\nThus, by reducing the percentage of exudate and granuloma in rat models of\ninflammation, P. quinquefolia<\/em> demonstrated its anti-inflammatory\nproperties. Moreover, it markedly decreased serum levels of IL-6 and TNF-\u03b1 65<\/sup>.<\/p>\n\n\n\n

Antimicrobial activity<\/strong><\/p>\n\n\n\n

The\nethanolic extract of P. quinquefolia<\/em> roots functions as an antifungal\nagent against different fungal species like yeast candida<\/em> and Aspergillus\nniger<\/em>. Furthermore, it is used as an antibacterial agent against\ngram-positive bacteria like Staphylococcus aureus<\/em>, Streptococcus\npyogenes<\/em>, and Bacillus subtilis<\/em>, and also\nagainst gram-negative bacteria like Salmonella typhi<\/em>, Pseudomonas\nfluorescence<\/em>, and Klebsiella pneumonia<\/em> 21<\/sup>. Aeromonas<\/em>\nhydrophila<\/em> and Aeromonas caviae<\/em> were significantly suppressed by P.\nquinquefolia<\/em> aqueous extract, with 59.68% and 55.90% inhibition,\nrespectively, in a study on antibacterial activity 66<\/sup>. Therefore, P.\nquinquefolia<\/em> evolves broad-spectrum activity against bacteria; again, this\nsupports the traditional use of the plant.<\/p>\n\n\n\n

Antioxidant activity<\/strong><\/p>\n\n\n\n

The\nethanolic extract of P. quinquefolia<\/em> bark and stem demonstrated a robust\nprotective effect against free radicals, including reactive oxygen species\nproduced in humans by both endogenous and external sources. The main factor\nstimulating many diseases is oxidative stress, such as degenerative and chronic\ndiseases like diabetes mellitus, cardiac conditions, atherosclerosis, cancer,\nand immunosuppression 67, 68<\/sup>. As a result, antioxidants are the most\neffective at eradicating free radicals 69<\/sup>. On the other hand, the\nchloroformic extract of the leaves and berries revealed such high free\nradical-scavenging activity. These findings support the plant’s traditional\nusage in treating dangerous human ailments 19<\/sup>.<\/p>\n\n\n\n

Another\nhexane extract study demonstrated the strong antiradical activity of P.\nquinquefolia<\/em> seed oil. The fatty acid content of the plant seeds, with\noleic acid (21.96%), palmitic acid (20.61%), and linoleic acid (48.23%) as the\nmain constituents, exhibits this activity 20<\/sup>.<\/p>\n\n\n\n

Medicine for treating eyelid eczema<\/strong><\/p>\n\n\n\n

Virginia creeper (P. quinquefolia<\/em>) is formulated in\ncombination with other plant materials (Artemisia rupestris<\/em>, saffron<\/em>,\nRubiaceae borreria stricta<\/em>, C. sativus<\/em>, Tea begonia,<\/em> and\nothers) to produce a medicine for eyelid eczema. That effect is exerted by\nprompting blood circulation, clearing toxins and heat, removing dampness, and\nmoisturizing dryness 70<\/sup>.<\/p>\n\n\n\n

Thrombin inhibitor effect<\/strong><\/p>\n\n\n\n

Serious coronary disorders such as myocardial infarction and\nstroke are highly affected by blood coagulation control, which may represent\nthe critical point in the treatment of these cases. The dichloromethane extract\nfrom P. quinquefolia<\/em> applies a new effective antithrombin natural agent\nidentified as amyrylhexadecanoate-amyrin 42<\/sup>.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Parthenocissus quinquefolia L.<\/em> is\na vibrant plant that produces a variety of valuable secondary metabolites such\nas stilbenes (trans-resveratrol, piceatannol, resveratrol 2-O-\u03b2-\nglucopyranoside, parthenocissins A, \u0263-viniferin, pallidol, cyphostemmin A, and\nmiyabenol C), polyphenolic compounds (phenolic acids like gallic acid, caffeic\nacid, chlorogenic acid coumaric acid, and flavonoids like quercetine-3O-\u03b1-L-rhamnoside,\nmyricetine-3-O-\u03b1-L-rhamnoside, quercitrin, rutin, quercetin, kaempferol,\nisorhamnetin, and luteolin), triterpene (\u03b2-Amyrine), fatty acids (palmitic\nacid, oleic acid, and linoleic acids), steroids (stigmasterol and \u03b2-\nsitosterol), an alkaloid (tropane alkaloidal compound in a glycosidic form), and\nothers (sennoside C, Asiatic acid or its analogue Madecassic acid, and the\ntriglyceride 1, 2-dipalmitoyl-3-oleoyl-glycerol). These important secondary\nmetabolites support the pharmacological activity of P. quinquefolia<\/em>,\nknown for its antioxidant effect, antimicrobial, anti-diabetic, thrombin\ninhibitor effect, medicine for treating eyelid eczema, and anti-inflammatory\neffect.<\/p>\n\n\n\n

Acknowledgments<\/strong><\/p>\n\n\n\n

The authors are deeply grateful to the College of Pharmacy,\nUniversity of Baghdad, for giving us the support to accomplish this work.<\/p>\n\n\n\n

Conflicts of\nInterest<\/strong><\/p>\n\n\n\n

There are no conflicts\nof interest.<\/p>\n\n\n\n

Funding Source<\/strong><\/p>\n\n\n\n

There is no\nfunding source.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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