MALVA: FOOD, MEDICINE AND CHEMISTRY

Plants of the genus Malva (Malvaceae) have been used by humans for millennia. In addition to being an important nutritional source, they are used for many medicinal purposes. Modern research not only supports the ethnomedicinal uses of these plants but has discovered many others. Many review articles were published about the traditional uses of Malva, and some reviews were published about modern research findings of the medicinal and other properties of M. sylvestris. However, none of the review articles discussed both traditional and modern scientific knowledge about all plants of this genus. In the present article an attempt has been made to discuss both the aspects comprehensively. Conclusions have been drawn and future research possibilities suggested.


Introduction
The genus Malva includes around 30 species. 1,2The plants originally grew in Eurasia and North Africa, but humans have taken them to all continents except the two poles.Archeological findings in Jordan indicate a continuous use of M. parviflora by humans since ancient times. 3xcavations in Isreal found an earlier use of M. parviflora and M. aegyptiaca dating around 23000 years before present. 4These findings were confirmed and expanded by recent two studies of the same site. 5,6Ancient Balkan inhabitants used Malva (unspecified sp.) as food sources and the materials of the plants were found in the remains of their teeth that go back at least 8600 years ago. 7e published literature about the Malva species is enormous but it focuses mainly on four of them: M. neglecta, M. parviflora, M. sylvestris and M. verticillata.The reported traditional uses and modern research findings of these species will be introduced in separate sections of this article, but they will be discussed jointly with the other species in the discussion section.Other species were little studied and for some others, there are no scientific publications at all.The last group includes M. aethiopica, M. assurgentiflora, M. brasiliensis, M. campestris, M. canariensis, M. dendromorpha, M. hispanica, M. microcarpa, M. microphylla, M. pacifica, M. preissiana, M. pseudolavatera, M. qaiseri, M. stipulacea, M. subovata, M. transcaucasica, M. tournefortiana, and M. trifida.
Many review articles were published about the traditional uses of Malva species and we will cite them here, but to the best of our knowledge, there are no published review articles that summarize the scientific literature about all Malva species that were studied so far.
M. verticillata was mentioned in a review article for its antidiabetic activity, 8 and wound healing potential of M. neglecta, M. parviflora and M. sylvestris was presented due to their anti-inflammatory properties. 9Antitussive activity of M. sylvestris was reviewed among other medicinal herbs that have the similar activity. 10A comprehensive review article about flavonoids in plants of the Malvaceae family (that includes the genus Malva) has been published recently and it shows some of the important natural products of this compound family. 11In Figure 1, the structures of selected flavonoids are presented.
M. sylvestris is the most studied species of the Malva genus so far.An excellent review of traditional uses (food, ethnomedicine) and scientific research findings of this plant was published by J. Gasparetto et al. in 2011. 12But it has three disadvantages.First, in terms of active natural products present in M. sylvestris, this review focuses only on polyphenols that are presented with structural formulae, while other compound families are mentioned but not presented like polyphenols.Second, a notable number of the cited references are patents that readers will not easily access.Third, despite being a very important research center of traditional uses and modern research of medicinal plants, Iranian publications are not sufficiently cited in this review.
Another review article that presents the biological activities of M. sylvestris was published by D. Paul. 13It presents some traditional uses of the plant and most of its modern research findings of medicinal and other activities very briefly.The phytochemical part is very short and presents mainly polyphenols.The author presents seven major biological activities of the plant while ignoring many others.Finally, a review article that includes both traditional uses and scientific data about the medicinal properties of the plant was published by Shokrollahi and Ali. 14Despite being supposed to include very much data, it presents it just partially and much of the known literature is not cited at all.

Traditional uses of Malva species
Three species possess the vast majority of publications, in terms of traditional-ethnobotanical uses viz., M. neglecta, M. parviflora and M. sylvestris.The details are presented in a separate tables (Tables 1-3), while the same about rest of the species are presented collectively in Table 4.  Turkey/Germany leaves Infusion: to treat abscesses, boils, swelling, insect bites, softening, antiseptic, astringent, abdominal pain, colic, otitis, asthma, constipation, colds, canker sores, 110 antiseptic for reproductive system 111

Palestine
Leaves Decoction: 10 g boiled in 100 mL of water, the affected is rubbed twice a day 117 Table 4. Traditional uses of Malva species (excluding subspecies in Tables 1, 2 and 3).

Malva species Country/Region Use (reference)
M. cretica Turkey Food 27

Spain
Infusion to treat colds, raw, immature fruits as food 35

M. nicaeensis
Turkey/Germany Leaves: To treat abdominal pains 15

Spain
Immature, raw fruits eaten as a snack 17

Lebanon
Decoction of whole plant used to treat arthritis 19 Italy Used against gastrointestinal pains, gingivitis, furuncles and wounds 23

Armenia
Cooked or raw as salad 40

Pakistan
Different parts are used to treat scurvy, piles, skin diseases, cough, bronchitis and inflammation of bladder 42

Slovakia
Food 95

M. rotundifolia
Italy Used for abdominal pains, burns, inflammations and soothing uterus 23

Arab countries
Many uses but this reference relates to M. sylvestris and M. rotundifolia together 74

Heavy metals accumulation
This plant accumulated Cd 2+ more than other plants that were growing near phosphate treatment industry in Tinisia.Average concentration in the stems: 28.9 ppm 135

Chemical composition and antioxidant activity
Chemical composition was analyzed by GCMS for volatile compounds, and metal ions concentrations were determined.Total phenolic content was found and tested for antioxidant activity (strong, DPPH) 136

Chemical composition, antioxidant activity, bread additive
Chemical composition was determined focusing on flavonoids, triterpenoids and fatty acids.Antioxidant activity was determined by (DPPH, Fe 3+ reduction).As bread additive, it was found to improve the quality and nutritional value 137

M. crispa
High protein content When cultivated protein content can reach up to 20 % (dried) 138 Flavonoids in flowers Various glycosylated falvonoids were isolated from the flowers of the plant and characterized by chemical analysis and spectroscopic methods 139

Synthesis of gold nanoparticles
Leaves of the plants were used as reductant in the synthesis of AuNP's from HAuCl4.These AuNP's were tested against food borne bacterial pathogens 140

Synthesis of silver nanoparticles
Aqueous extract (reductant) of the leaves of the plant was used to prepare AgNP's.These were tested against various pathogen bacteria and found effective. 141They were also highly toxic for zebra fish (Danio rerio) 142

Antiinflammatory and antioxidant
Ethanolic and aqueous extracts of seeds and aerial parts, as well as crude polysaccharides from cold and hot water extracts exhibited a significant anti-inflammatory and antioxidant (DPPH) activity 143

M. moschata
Antibacterial Hexane, dichloromethane and methonal extracts were prepared then the dry matter was suspended in DMSO.It was active against several types of bacteria 144

Plant pigments
This work focused on chlorophylls and carotenoids 145

M. nicaeensis Heavy metals accumlulator
Very good heavy metals accumulator from polluted soils, especially Zn and As.Promising bioremediation agent 146

Inhibition of pancreatic lipase
Dried aerial parts of the plant were extracted with methanol and the dry extract was suspended in DMSO and tested for PL inhibition.Strong activity 147

Inhibition of hormone sensitive lipase
Dried aerial parts of the plant were extracted with methanol and the dry extract was suspended in DMSO and tested for HSL inhibition.Strong activity 148

Polysaccharide isolation and activities
Water soluble polysaccharide was isolated and its monosaccharide units were determined (qualitatively).It was tested for anti-inflammatory activity (strong) 149

M. rotundifolia
Composition General composition was determined for macronutrients, fatty acids and some minerals.No alkaloids found 150

Antimicrobial
Ethanolic extract was dissolved in DMSO and tested for antimicrobial activity (very weak) 151

M. sinensis
Cadmium accumulation Contaminated soil from lead-zinc mines was treatred with this plant (also known as M. cathayensis) and found to be hyperaccumulator 152

Modern Research Findings
The Malva species very extensively researched by modern techniques also.However, like in traditional uses of these plants, the vast majority of publications focus on four species of this genus: M. neglecta, M. parviflora, M. sylvestris and M. verticillata.Summary of research regarding each of these species are presented in a separate table.Like in traditional uses, M. sylvestris is most studied is this respect also.

Malva neglecta
Malva neglecta is a widespread edible plant that can be found in Eurasia and North Africa.It has many common names, sometimes in the same culture, and this might be misleading.Modern research findings approve its known traditional medicinal properties, and it is being studied more and more.A summary of these findings is shown in Table 6.

Malva parviflora
Malva parviflora is the second most widely studied Malva species after M. sylvestris.Despite the fact that its natural habitat overlaps with that of M. sylvestris and M. nicaeensis, it is relatively easy to distinguish M. parviflora from the other two: its leaves are more cycle shaped than of the other two species, and the plant itself is much lower than the two others.Modern research started studying M. parviflora only in the last four decades and the major findings are summarized in Table 7.

Malva sylvestris
Malva sylvestris is the most widely studied species of the Malva genus, and one of the most studied in the whole plant kingdom.In most parts of its natural habitat, it is very widespread, and most people mean it when they mention the words Malva, mallow or Khubbaiza in the Middle East.Modern reported literature about this plant is very large and published regularly.We have tried here to cite most important publications and summarized them in Table 8.We have cited together publications, published in the last twenty years (as of 2008), that report the same property.If notable differences are presented, the publications has been cited separately.

Malva verticillata
Among the four major Malva species listed in Tables 6-9, M. verticillata is the least investigated and modern research publications about it are fewer.In addition, traditional uses of this plant are also fewer than the other three.Despite this, a very comprehensive work has been carried out by studying the chemical composition and biological activities of seeds.This exceptional work was done by a Japanese group lead by M. Tomoda and was published in nine articles between 1987 and 1992.This work has been presented collectively.
It is also notable that M. verticillata seeds are rich in polysaccharides that were thoroughly studied.It is interesting to pay special attention to the antidiabetic activity of M. verticillata, as this activity is one of the major properties of this plant.

Discussion
While studying the literature of traditional uses of Malva species, we found that some of them are in an ambiguous status as for their distinctiveness.For example, two of these species are M. alcea and M. excisa. 353So, despite the fact that M. alcea was mentioned with other known Malva species (Crispa, Pussila and sylvestris) as having traditional antiviral infections activity of humans and animals, 354 we did not include this paper in Tables 3 and 4.
Al-Asmari et al. from Saudi Arabia reported that in ethnobotanical medicine of their country, leaves of M. parviflora are used to treat "scorpion sting envenomation." 71hey also cite another publication that is supposed to support their claim. 355But reading this reference carefully reveals the fact that either the report or the citation or both are wrong: in reference 355 there is no mention of "Malva" and/or "parviflora", and authors indicate Eryngium creticum Lam. as a plant that is used in traditional Palestinian medicine to relieve pains of scorpion stings and snake bites.
Malva species are used for dye production. 102The colored compounds of these plants, especially flavonoids/anthocyanins are the major source for these colors.
These compounds are naturally produced (see Figure 1), but this production can be enhanced by irradiation of the plants with UV, 285 or by the addition of other growth promoters.These results were confirmed by later publications. 287,288J. Pinela and his colleagues from Portugal reported using Gamma radiation for the same purposes in M. neglecta. 356Scientifically speaking, new results were obtained, and this report should be included in Table 6.We did not include it there for two reasons.One, this method is very expensive, and two, there are no follow up studies about the effect of this powerful radiation on other compounds in the plant, and maybe diverse results in terms of toxic materials production.
One of the very interesting medicinal activities of Malva plants is their potential use as antiobesity agents.In most publications, this activity is mentioned or studied along with the antidiabetic activity.M. sylvestris is traditionally used for this matter (weight loss) in Iran, 101,103 and this use is not "very unusual and rarely mentioned," as Menale and Muoio indicated. 106Modern research found a possible explanation for this potential activity of Malva species.Y. Bustanji et al studied the antiobesity activity of M. nicaeensis, through the inhibition of pancreatic lipase (PL) and hormone sensitive lipase (HSL). 147,148PL inhibition was also reported by M. neglecta. 171These studies suggest the importance of followup studies on this subject.
Ameri et al indicated that the common name of M. sylvestris is "Jews mallow". 114This is not correct because it refers to "Mulukhiyah" or Corchorus olitorius, a plant in the Malvaceae family but to the genus Corchorus not Malva.
Variations in chemical compositions of plants due to various factors such as locations, seasonality and weather conditions, are well known and widely reported.But such variations can also result not only from these external effects, but they can also result from internal factors of the plant e.g., the stage of growth or plant part.An interesting example of such variations has been reported by Zouari et al. 136 Figure 2. Compounds with notable concentration variations in M. aegyptiaca according to growth stage or plant part 136 They have reported the different concentrations of volatile compounds according to three growth stages of M. aegyptiaca and also the concentration differences of macronutrients, metal ions and volatile compounds in leaves and fruits.Some of these compounds are presented in Figure 2, had notable variations according to growth stage.
Tunisian group lead by N. Zouari, published earlier this year another study 137 completing their previous report and evaluating the importance of M. aegyptiaca as bread additive.One of the interesting compounds they found was malvasterone (Figure 3), a steroidal triterpenoid that was first isolated from the roots of M. parviflora. 357Steroidal units were also isolated later from M. sylvestris (Figure 3). 286hese have an interesting lactone sub-unit, which grant them additional potential activities.303][304] In all these reports, aqueous extracts of leaves or flowers of the plants were used.The major quality that enables this kind of uses and reactions is the fact that these extracts are rich in flavonoids and anthocyanins.These compounds are good reductants, especially when hydroxyl (OH) groups are present in their structures. 358yrami-Miavagi and his colleagues, 164 have reported two properties of M. neglecta, antioxidant and contraceptive, as a safe alternative to prostodin (synthetic contraceptive), which causes oxidative stress and other damages in urinary system.There is no question about the antioxidants of Malva plants, but our intense search for research reports that support contraceptive activity of these plants was in vain, despite the fact that other plants with this activity are well known. 359,360,361

M. sylvestris
The de-epoxidation of violaxanthin to zeaxanthin (Figure 4) is a biologically important process since it prevents photooxidative damages that might be caused to chloroplasts by excessive radiation. 362

Figure 4. De-epoxidation of violaxanthin to zeaxanthin
This process occurring naturally has an additional importance when leaves of this plant are consumed as food since health benefits of zeaxanthin are more than those of violaxanthin.So it is favorable to expose leaves of the plant to light before cooking.
There seems to contradiction in two reports presented in Table 7 regarding the antidiabetic activity of M. parviflora.Phoboo 202 reported weak activity, however, strong activity has been reported by El-gizaewy. 204e can identify three sources of the difference.First the part of the plant used, leaves and seeds respectively; secondly, extraction solvent, water and n-hexane, and finally the testing model, in vitro enzyme inhibition (-amylase and -glucosidase) and in vivo treatment of streptozotocin (STZ) induced diabetic rats.Isolation, characterization and three biological activities of a novel, natural derivative of the triterpenoid oleanolic acid has been reported. 210Comparing the structures of oleanolic acid and the new compound (Figure 5), clearly shows that this derivative includes more polar functional groups.

Figure 5. Oleanolic acid and its novel, natural derivative reported in reference 210
Oleanolic acid itself is physiologically very active compound, 363 and this new derivative should also be additionally studied and chemically modified to prepare new derivatives and test their activities.
Toxicity of Malva species to animals is very rare but was indicated in the research literature.M. neglecta was reported to cause hypocalcemia in cow, 205 but the mechanism of poisoning action was not reported.A controlled study with horses showed that consumption of large amounts of M. parviflora resulted in energy balance damages. 213It is proposed that cyclopropene fatty acids contained in the plant are responsible for this, and elevation of acylcarnitine (Figure 6).

Figure 6. Structures of malvalic and sterculic acids and carnitine
Authors explain their findings by the rapid and easy oxidation of the unstable cyclopropene ring, which is consistent with earlier reports. 364 2006, Ganai et al reported a detailed method of isolation and purification of the enzyme sulfite oxidase from leaves of M. sylvestris. 228This work completes an earlier work by this author (and others), but we did not cite it in Table 8 due to its partial findings. 365Sulfite oxidase catalysis the oxidation of sulfite to sulfate and it has very important role in sulfite detoxification in plants. 366rmination inhibition of plants by other plants is known as allelopathy.Many plants act as allelopathic for another plant and their growth can be inhibited by other plants.
Cutillo and her colleagues found that two new terpenoids that they isolated from M. sylvestris and characterized have an allelopathic effect on Lactuca sativa. 229The structures of these compounds are shown in Figure 7.Such findings are consistent with earlier and later reports of allelopathic effect of terpenoids on L. sativa. 367und healing and treatment of skin diseases by plant extracts and other pharmaceutics is a known phenomenon and has been extensively studied and published. 368Plants of the Malva genus are among the most active as regard this activity.9][250][251][252][253][254][255][256][257][258] But carefully reviewing this data reveals an interesting and not always consistent results.For example, it is reported that chloroform and n-hexane extracts of M. parviflora are irritant. 183However, others found counter-irritant activity in chloroform and other extracts of the same plant. 369Moreover, chloroform extract of M. sylvestris was also reported as having wound healing activity. 249,250These contradictions must be resolved by future more extended studies.
Mineral content of Malva species has been published in several research articles.There is a common result in all of them.The genus Malva is rich with potassium and calcium (M.neglecta; 150 M. parviflora; 201 M. sylvestris 223,229,260,262,263 ).Several methods were used to determine the metal content and one of the best, yet simplest was reported by S. Terfi and his colleagues. 264Related to that, some studies were conducted to test the capacity of Malva species to accumulate heavy/toxic metals from contaminated soil or aqueous solutions.We present the results of these publications in Table 10.

Methods and major findings (reference)
Chemical composition Alkaloids, flavonoids, saponins are present but tannins are absent. 153

Antioxidant activity
Moderate activity was detected in methanolic and aqueous extracts DPPH and TBA methods. 154

Poisoning
Hypocalcemia reported in a cow which ate a large amount of the plant. 155

Antibacterial
Ethanolic extract of flowers was tested against 10 types of bacteria.Six of them were resistant 156

Antibacterial
Aqueous, ethanolic, chloroform and acetone extracts show moderate activity against four types of bacteria. 157

Antimicrobial
Aqueous, methanolic, n-hexane, chloroform, ethyl acetate and n-butanol extracts did not show any activity against four types of bacteria. 158

Antioxidant
Stong antioxidant capacity of the phenolic content. 159

Antibacterial
Aqueous, ethanolic and chloroform extracts of M. neglecta and M. sylvestris were tested against seven types of bacteria that cause wound infections.All extracts were active, and ethanolic was most active for both plants.Extract of M. sylvestris was more efficient 161 Mineral content K + was highest with 230 mg kg -1 162 Antiinflammatory Methanol extracts show moderate activity against some types of inflammation. 163

Contraceptive
Female rats were treated with hydroacoholic (1:8) extract and prostodin, a synthetic contraceptive.The extract caused lesss oxidative stress and other damages in kidneys and urinary space 164 Kidney stones preventive Production of kidney stones (CaOx) and tubulointerstitial damage, induced in male rats by ethylene glycol and ammonium chloride, was reduced on treatment with aqueous extract of the plant. 165

Antiinflammatory
Aqueous extract was tested against various inflammatory agents in patients with osteoarthritis and found as potent inhibitor 166

Antibacterial
Ethanolic extract found active against antibiotic-resistant S. aureus 167

Mucilage uses
Mucilage was separated from fresh leaves and precipitated by acetone, contains carohydrates and flavonoids.It was used to bind the synthetic analgesic of diclofenac sodium and produce granules 168

Antioxidant
Hydrocolloid water extract of plant leaves was prepared in various temperatures (55-95 C).The products of higher temperatures showed excellent antioxidant activity (DPPH) 169

General composition, antioxidant, antibaterial
General composition of fresh leaves was determined by three classes of components: macronutients, metals and total phenols.The methanolic extract was tested for antioxidant and antibacterial activities: both were found moderate comparing with other plants in this study 170 Health benefits, antioxidant and enzymes inhibition This study connects the traditional known health benefits of the plant (very good food photos) and its medicinal properties.Aqueous extract showed antioxidant activity and pancreatic lipase and glucosidase inhibition 171

Synthesis of silver nanoparticles
Aqueous extract was used as a reductant in the synthesis of AgNP's from silver nitrate 172 Composition, anticholinesterase, antimicrobial, antioxidant, aflatoxin content The aqueous extract was analyzed by LC-MS/MS for total phenolic content and determination of single phenolic compounds.It showed anticholinesterase, antimicrobial and antioxidant activities, and no aflatoxin content.The essential oil was analyzed by GC-MS for fatty acids content and volatile compounds 173

Property Methods and major findings (reference)
Thiamine content and safety to ruminants Thiamine content of the plant is relatively high compared with other plants in this study.This is in accordance with very low levels of thiamine destroying enzyme, thiaminase, that consumption of large amounts of it may lead to cerebrocortical necrosis in ruminants. 174

De-epoxidation of in leaves
Temperature and light (=505 nm) on the de-epoxdation of violaxanthing to zeaxanthin.Leaves were sensitive to radiation and less to temperature, especially under 24 C. 175

Antifungal proteins
Two antifungal proteins were isolated and characterized from seeds of the plant.The proteins were found fungisatic instead of fungicidal. 176

AChE inhibition
Ethanolic extracts of leaves are better inhibitor of acetylcholine esterase (AChE) than aqueous extracts and most efficient concentration was 0.025 mg ml -1 . 177

Antibacterial, antiinflammatory
Extracts of plant parts showed antibacterial and anti-inflammatory activities.Authors suggested synergism of two unidentified anti-inflammatory compounds. 178

Proximate composition, antioxidant
Protein, total phenolic content and metal content was determined.The plant is calcium rich.80% Aqueous methanol extract showed moderate antioxidant activity (DPPH). 179otal phenolics, antioxidant Total phenolic content was detemined and two of their sub-classes.Ruduction power (Ferric ion) and DPPH, ABTS quenching capacity were also determined 180 Anti-inflammatory, anti-allergic Aqueous extract of the flowers found active againts allergen-induced eosinophilia 181 Anti-inflammatory, analgesic Methanol extract of aerial parts has anti-inflammatory and analgesic activities.182 Antibacterial, antifungal, irritant Hexane, chloroform, ethanol and aqueous extracts showed antibacterial and antifungal activities.
Most extracts had irritant effect on inner surface of ear of male albino rabbits. 183nti-inflammatory, antioxidant, metal chelating Methanolic extract had stronger anti-inflammatory activity.Methanolic and aqueous extracts showed strong antioxidant (DPPH) and ferrous ion chelating activities. 184hytochemical screening, antioxidant Fresh leaves and stems were found to contain phenols, flavonoids, sponins, alkaloids, resins and tannins.Aqueous extract of both parts had antioxidant activity. 185

Antioxidant
Ethanolic extract of leaves had strong antioxidant activity. 186

Hypoglycemic
Extract of aerial parts showed promising antidiabetic activity. 187

Silver nanoparticles preparation
Fresh leaves were extracted with 70% ethanol/water and the extract was used as reductant in synthesis of AgNP'S from AgNO3. 188

Phytochemical analysis
Seven phytosterol, two polyphenols and 14 fatty acids were identified from 85% ethanol extract.Alcoholic extract had significant anti-inflammatory and cytotoxic activities and aqueous extract antimicrobial activity. 189

Phytochemical analysis
Very partial phytochemical analysis of aerial parts that were extracted with chloroform. 190oxicity to Flour beetle Ethanolic (see remarks in the discussion section) extract of leaves was prepared and found fatal for the larvae of Tribolium confusum 191

Growth promoter
Aqueous extract (plant part/s not indicated) promoted the growth of cowpea (Vigna Unguiculata) 192

Cytotoxicity
95% Ethanolic extract showed weak activity against breast cancer cell lines. 193

Hepatoprotective
Whole plant was extracted by 70% ethanol/water.The extract was analyzed for major chemical constituents and tested against paracetamol induced hepatotoxicity: very active 194

Pharmacognostic variables
Pharmacognostic variables were determined for all parts of the plant in order to standardize herbal medicines data. 196

Heavy metals accumulation
Heavy metals concentrations was determined in aerial parts of the plant grown in normal soil.
Results showed that heavy metals did not exceed healthy limits. 197,198il contamination removal Soil was contaminated with oil (0.1 and 0.5%) and was treated by the plant for oil removal.After 30 days, 88.5% of the oil was removed. 199

Adsorption of Cr(III)
Conatminated water with Cr(III) was treated by inserting the plan's roots in and the concentration change was measured under various pH and temprature values.Moderate activity 200

Nutrients, antioxidant
Major nutrients, minerals, total phenolic content and anthocyanins were determined in aerial parts.High ntioxidant (DPPH) activity 201 Antidiabetic, antioxidant, antihypertensive Watet extract of aerial parts was prepared and its major chemical constituents were determined.It was tested for antidiabetic (weak), antioxidant (moderate) and antihypertensive (very weak) activities 202 Drying process effect on content Leaves were dried by four methods and total phenolic content and antioxidant activity of the products were determined 203 Fatty acids content, antioxidant, antidiabetic Dried seeds were extracted by n-Hexane to prepare fixed oil.The fatty acid content of this oil (9, saturated and unsaturated) and its antidiabetic (high) and antioxidant (high) activities were determined 204 Antiprotozoal, antimicrobial 75% Ethnol/water extract of the leaves was tested for antiprotozoal and antimicrobial activities.It showed moderate antimalarial and high anti-leishmanial and weak antimicrobial activities 205,206 Ulcerative colitis inhibition Methanolic and aqueous extracts were prepared from leaves.Methanolic extract was more efficient in attenuating inflammation and tissue damage induced acetic acid 207 Growth inhibition by eucalyptus leaf extract Eucalyptus leaves aqueous extract was found relatively effective but only in high concentrations as herbicide against seeds (germination control) and adult plants of M. parviflora. 208

Antioxidant
This study combines ethnobotanical uses (Brazil) and antioxidant (3 methods) test of the aqueous extract of leaves: high 209 Hypolipidemic, hypoglycemic, anti-inflammatory, A novel triterpenoidic acid, 2,3,23,29 tetrahydroxyolean-12(13)-en-28-oic acid was isolated and was found to have hypolipidemic, hypoglycemic and anti-inflammatory activities. 210emory retention 80% Ethanol/water extract showed memory retention in mice. 211β-sitosterol, antibacterial Chloroform and ethanolic extracts of roots showed high antibacterial activity against small number of bacteria.It is suggested that β-sitosterol in chloroform extract is the active compound 212

Horse poisoning
Four horses, fed with large amounts of the plant, had myocardial disease and myopathy compared to control.Cyclopropene fatty acids in the plant may cause negative energy balance and abnormal acyl carnitine profiles. 213

Zinc accumulation
High concentrations of Zn were found in roots but not aerial parts of the plant that grew around steel industries. 214

Cd, Cu accumulation
Plants irrigated with sewage water, accumulated copper and cadmium up to six folds compared with control. 215old nanoparticles 70% Ethanol/water extract of the plant was used as reductant in the synthesis of AuNP's from HAuCl4 216 Glucoronides (glucosyl derivatives) of various flavonoids from leaves of the plant, including a glucoronide sulphate 217,218 Anti-complementary mucilage Water extraction of fresh leaves afforded mucilage with average molecular weight of 6x10 6 .It consists L-rhamnose, D-galactose, D-galacturonic acid and D-glucurnic acid, with molar ratio of 6:3:2:2, respectively.This mucilage has anti-complementary activity 219
No activity reported 222

Mineral content
Mineral content was determined from plant ash by means of atomic absorption.Among studied seven edible plants, M. sylvestris had the highest content of phosphorus and potassium 223 Radical scavinging, Fe(II) chelating 50 % Methanol/water extract was tested for antioxidant activity (DPPH, H2O2) using low concentrations of the extract.For DPPH test it was inactive and for H2O2 it had moderate activity.Fe(II) chelating high 224 Anthocyanin inhibibs lipid oxidation "Homemade" anthocyanin samples from the plant were tested for radical scavinging in high fat albino rats.In concentration of 0.2 mg mL -1 it showed very strong activity of plasma lipid oxidation inhibition 225 Anthocyanin antibacterial activity "Homemade" anthocyanin samples from the plant were tested against several types of bacteria, and found active against some of them 226

AChE inhibition, antioxidant
Ethanolic extract was prepared from aerial parts and tested for acetyl choline esterase inhibition: active only in high concentrations.Antioxidant activity was high 227

Sulfite oxidase purification and kinetics
Sulfite oxidase was purified from leaves by acetone fractionation, heat treatment and several analytical methods.The kinetics, optimal pH, optimal tempretaure and the activation energy of the ezyme activity were detemined 228 Novel terpenoids, growth inhibition of Lactuca sativa Novel terpenoids (Figure 7) and other known were isolated from the aqueous extract.The new compounds were tested for germination inhibition of L. sativa and found moderately active 229 Malvone A, antifungal New phenolic 1,4-quinone (malvone A, Figure 7) was isolated from the stem bark by aqueousacetone solution that contains ascorbid acid.The synthesis of malvone A in the plant was enhanced by plant pathogen Verticillium dahliae and it has antifungal activity against the same fungus 230 Alkaloid content Total alkaloids content was isolated from methanolic extract that was treated by acid then base: 35 mg in 100 g plant aerial parts 231 Antiproliferative (inactive) 70 % Ethanolic/water extract of leaves was tester for antiproliferative activity against four types human tumor cell lines: inactive.n-hexane fractionation yielded campesterol, stigmasterol and sitosterol 232 Effect of aqueous sulfur dioxide Treating the plant leaves with various concentrations of aqueous sulfur dioxide solution resulted in decrease of all biochemical activities especially antioxidant capacity 233

Immunomodulatory
Carbohydrate rich water extract was tested for immunomodulatory activity in BALB/c mice and found active in some test types 234 Anti-inflammatory, antioxidant 70 % Ethanolic extract was prepared and fractionated with 90 % CH3OH and n-hexane.Tests showed antioxidant (DPPH) and anti-inflammatory (croton oil-induced ear oedema in mice) activities 235

Anti-inflammatory
In the tests of cream prepared from water extract of aerial parts 236 and 70 % ethanol extract of flowers 237 against carragenin-induced edema in rats, and in tests of ethanolic extract of leaves against 12-O-tetradecanoylphorbol-acetate induced in mice active compounds were indicated.Quantification of prostaglandin by LC-MS/MS validated the tests of ethanolic extract of leaves was tested against activity of various inflammatory agents. 239Different fraction of ethanolic extracts of leaves were tested against A. actinomycetemcomitans. 240

Antinociceptive
Leaves water extract was not found active by hot-plate model against four pain agents, writhing test, neurogenic and inflammatory phases of formalin model, capsaicin-induced pain. 241

Anti-inflammatory, antiulcerative
Aqueous extract of aerial parts showed anti-inflammatory and anti-ulcerative activities in rat model (drinking water) 242

Antioxidant
Aqueous extract of leaves was tested for antioxidant activity (DPPH, superoxide radical), then analyzed to yield eleven active compounds, that each one of them was tested. 243Total phenolic content and antioxidant activity (three methods: FRAP, DPPH, TAC-Mo VI ) of leaves (highest), stems and seeds. 244Total phenolic content and antioxidant (DPPH) activity were determined for methanolic extract of whole plant. 245Methanolic extract of leaves was teasted for antioxidant activity (DPPH). 246Methanolic (with ammonium citrate) of aerial parts was teasted for antioxidant activity (DPPH) 247

Skin disorders and wound healing
Burn wounds in rats were reated with diethyl ether extract of flowers, resulting notable healing. 248xcision wounds were treated with chloroform extract of flowers, resulting wounds healing. 249,250ifty patients with hand eczema treated with ointment showed partial healing and no adverse effects. 251Alloxan-induced diabetic rats with blade injury 252 and burn injury 253 showed complete and 80 % healing on treatment with dietheyl ether extract of flowers for 18 days.Blade-induced injury in palatal mucosa of rats showed on healing effect of 70% ethanol/water extract of stems and leaves. 2540% Ethanol/water extract of flower was prepared as cream with 5 and 10%.It was tested for treatment of burn (hot plate) injuries.Complete healing after 35 days. 255Polyherbal cream (PHC) that contains aqueous extract of leaves was used to treat second-degree burn wounds in rats (110C, 10 s).After 14 days, 87% of the wounds healed.Total phenolic content, antimicrobial and antioxidant activities PHC were determined. 256A cream (1%) was prepared from aqueous extract of flowers used to treat surgical blade induced wounds in mice.After 10 days healing was almost complete. 25740% Ethanol/water leaves extract was used to treat inflammation (formalin induced) and tested for linear incised wound healing in rats and found effective 258 Metal ion composition and heavy metal accumulation Calcium and potassium were found in relatively high concentrations in leaves. 259Unspecified plants showed high concentrations of calcium and potassium after burning. 260Accumulation of major elements and heavy metals in plants (aerial parts) grew in industrial contaminated soil.The plant was classified as hyperaccumulator. 261Concentrations of metals in leaves were measured in populated areas.Results are around standard except lead which was higher. 262Metal composition of edible parts was determined by inductively coupled plasma optical emission spectroscopy.Results showed that washing the plants as done before cooking, reduces the content of metals notably. 263This study reports three methods of extracting toxic metals from the plant leaves, finding that dry ashing method using 4:1 HNO3:HCl was most efficient. 264Dried flowers were sieved in different meshes and used as green biosorbent of Pb(II) from aqueous solution.Maximum biosorption capacity was 25.64 mg/g. 265Dried leaves were powdered and dried again and the resulting mesh was used to Hg(II) from aqueous solutions comparing with charcoal and found more efficient. 266Synergism of plant powder and charcoal yielded high removal of Hg(II) from aqueous solutions 267 Antimicrobial, antibacterial, antifungal Whole plant extract (96% EtOH/Water, traditionally used to treat gastrointestinal disorders) found active against Helicobacter pylori. 268Methanolic extract of aerial parts and three fotmulations of it were tested against several bacteria.The extract was very active gainst S. aureus. 269n-Hexane, dichloromethane and methanolic extracts of leaves and flowers were prepared (separately) and tested for antimicrobial and and antifungal activities.Only methanolic extract was active. 270Tincture (no preparation method) was most active among other plants, against Candida albicans and C. tropicalis. 271This study tested the components antimicrobial activity of commercial mouthwash Malvatricin: tyrothricin, hydroxyquinoline and the plant tincture.It revealed that activity is only a result of hydroxyquinoline presence. 272Aerial parts were extracted with 50% methanol water and the extract was tested for urease inhibition: weak. 273Methanolic extract of leaves was tested for urease inhibition (moderate) and against Helicobacter pylori: inactive. 274Aqueous, ethanolic and n-hexane were prepared and tested against oral bacteria: inactive. 275Roots were extracted with 48% EtOH/water and tested against oral Streptococci bacteria and found active against some of them. 276cetone/water (7:3) extract was tested for antifungal activity (moderate) and analyzed for major compound families and some single active compound. 277Ethanol/water (7:3) extract of aerial parts was tested for antibacterial activity: active against Pasteurella multosida, inactive against Salmonella enteritidis. 278Aerial parts aqueous extract was tested against Candida albicans infection in mice and found moderately active. 279Vaginal protection medical products based on extracts of the plant (with extract of Calendula officinalis) are used, especially in pre-pubertal age. 280Aerial parts 96% ethanol/water extract was tested against Candida albicans infection in mice and found moderately active. 281Leaves were extracted with 3:1 methanol:water and the extract was tested against four types of bacteria: inactive. 282Aqueous and ethanolic extracts of all parts were prepared and tested against C. albicans biofilm formation.All extracts were active but most active was the ethanolic extract of roots 283 Chemical composition and some related properties Methanolic extract of aerial parts was tested with four methods for antioxidant activity.Chemical composition was determined on three levels: macrontrients, major compound families and major compounds in each family. 284Anthocyanin production was increased by UV irradiation of the flowering plant. 285Three steroidal lactones and three glycosyl derivatives were isolated and characterized from methanoic extract of the friuts (see Figure 3). 286Silver nitrate, abscisic acid and UV-B radiation used as growth-stressers and had different effects on growth of the palnt, but they all increased anthocyanin production. 287Same findings of previous publication concerning silver nitrate. 288Leaves and petioles methanol extract was analyzed (GCMS) for proximate composition: fatty acids, metal ions, total flavonoids and mucilage.The antioxidant capacityof the extract was tested by four methods. 289Lipid content of seed oil (extracted with petroleum ether) was determined by GCMS for saponifiables (fatty acids by preparation of their methy esters) and unsaponifiables (mainly phytosterols).The antioxidant of the oil was determined by DPPH assay. 290Ethanolic extract (plant parts not indicated) was tested fot antioxidant activity (DPPH) and partitioned with other solvents.Total content of the following compound families was determined: free monosaccharides (none), saponins, tannins (very low), terpenoids (very low), flavonoids and alkaloids. 291Etherial, aqueous and ethanolic extracts of seeds and stems (separately) of the plant were prepared, and were for main compound groups (phenolics, flavonoids, alkaloids …etc.).Then they were analyzed by TLC and some known compounds were identified. 292Essential oil of flowers was extracted by hydrodistillation and analyzed by three sucessive methods, identifying volatiles and odor activity values: -damascenone was highest. 293Total phenolic content in aqueous and ethanolic extracts (plant parts not indicated), as well as quantitative analysis of the extracts by HPLC.All known compounds. 294Qualititaive analysis of fruits by extracting with several solvents and detection of the content of major compound families. 295Crude fiber content of stems and leaves was determined, along with influences of locality an seasonality.The isolated crude fiber was fed to rat causing an icrease of faecal weight, indicating laxative activity. 296Whole plant (before flowering) was extracted with acetone/n-hexane (1:1) and analyzed by GCMS for poly aromatic hydrocarbons (PAH's) and poly chlorinated benzenes (PCB's), in plants that grew in contaminated soils.PAH's were below detection limit but PCB were accumulated in the plant. 297Flowers were extracted with methanol and total phenolic content, saponins and alkaloids were determined.The antioxidant of the extract was tested by several methods. 298Ethanolic extract of flowers was analyzed for total phenolic content, total flovonoids, anthocyanins, carotenoids and fatty acids.Antioxidant activity of the extract was tested (4 methods, high) and hypoglycemic activity (α-amylase and α-glucosidase inhibition, very high) 299 Polysaccharides and their properties Leaves were extracted with 80% EtOH/water and extract fractionated to yield polysaccharides.No analysis for monosaccahrides is reported but detailed theoretical is presented for extraction and antioxidant activity of the polysaccharides. 300Aerial parts was sequentially extracted with n-hexane, ethanol and water to yield 9.6% polysaccaride, which consists galactose, glucose, uronic acids, arabinose, and rhamnose (4:5:14:6:1, MW= 1.3x10 6 KD).The polysaccharide has antiulcerative activity in rats. 301Leaves enzyme (cellulase) assisted extraction of some polysaccharides.Theoretical is presented and antimicrobial, antitumor and antioxidant activities are reported 302 Nanoparticles, synthesis, uses Leaves aqueous extract and CuCl2 were used to prepare CuONP's and their antibacterial activity was tested. 303Leaves aqueous extract and AgNO3 were used to prepare AgNP's and their mosquito larvicide activity was tested.These AgNP's have almost no effect on other aquatic organisms 304

Antioxidant applications
Aqueous decoction of leaves and flowers was prepared and tested for antioxidant activity (DPPH, NBT) and gainst ammonium metavanadate (NH4VO3) kidney toxicity in rats. 30580% Methanol/water extract was prepared (plant part not indicated) and its antioxidant activity (DPPH, fenton reagent) was determined.Also, protection of fatty acids was measured in vitro 306 Sedation, anti-anxiety, anesthetic, radiation side effects relief, anti-seizure Methanol:chloroform (7:3) extract was prepared from stems and leaves.It was tested in rats for sedation, pre-anesthetic and anti-anxiety effect compared with with diazepam (valium, stronger) 307 Patients with radiation therapy of prostate cancer and experiencing severe dysuria, were treated with plant powder (parts not indicated), showing notable improvement of pain relief 308 Plant powder (parts not indicated) were extracted with 85% ethanol/water.The extract was found anti-seizure active in PTZ-induced seizure models on mice 309 Equal portion of the powder of the M. sylvestris and Alcea digitata (plants parts not reported) were used to treat patients with xerostomia (dry mouth) after radiotherapy of head or neck cancer. 310Hydroalcoholic extract (no ratio, no plant parts) was used to treat mice with convulsion induced anxiety. 311Whole plant aqueous extract was found protective against UV-B radiation in mice. 312nzyme related activities Methanol:water (4:1) extract was prepared (plant parts not indicated) and was tested for angiotensin converting enzyme (ACE) inhibition: moderate. 313Catalase was partially purified and immobilized onto chitosan and its catalytic properties were studied 314 Interaction with drugs and toxic compounds Aerial parts aqueous extract was administered to Leghorn chickens along with Bromhexine HCl.The extract reduced the adverse side effects of the drug. 315Whole plant was extracted with 95% aqueous methanol and the extract was tested against paracetamol-induced hepatotoxicity and found significantly active 316 Most (87%) patients at basic health units in Brazil reported using M. sylvestris products as an alternative and complementary therapy 317 Leaves aqueous extract ameliorated motor asymmetry in rats induced by 6-hydroxydopamine but had no protective effect neurons 318 50% Methanolic (water) extract was prepared, analyzed for major compound families, minerals and tested for antioxidant activity (2 methods).Also, it was tested for reduction of lithium carbonate damages (oxidation, body weight gain, kidney) in rats: very positive 319 50% Methanolic (water) extract was prepared, analyzed polysaccharides and tested for Fe(II) chelating and antioxidant activity.Also, it was tested for reduction of lithium carbonate damages (heart, testicles) in rats: very positive 320 Ethanol-water (4:1) extract was tested against sodium fluoride nephrotoxicity and found active 321

Constipation relief
Flowers aqueous extract was administered to people with constipation and stool problems, Constipations decreased and stool form changed from hard to normal (self reported). 322Constipation in rats was induced by loperamide and treared with leaves aqueous exreact and yohimbine as control laxative (see Figure 8) 323

Mouth and throat diseases
A herbal mouthwash consisting of Althaea officinalis, Salix alba and M. sylvestris leaves (ratio, 5:1.25:1, respectively).Leaves extracted with ethanol and the dry extract was suspended with water (0.31%).This suspension was used to treat people with chronic periodontitis and using chlorhexidine as control, and positive results were obtained. 324Flowers 95% ethanol/water extract was tested for sore throat treatment: inactive 325

Corrosion prevention
Leaves methanolic with metal corrosion prevention activity was analyzed to determine major compounds responsible for this activity: furfural; levoglucosenone and Levoglucosan, two seven membered multi oxygenated heterocycles; 1,4:3,6-Dianhydroalpha-d-glucopyranose, six membered multi oxygenated heterocycle 326 Functional foods for pets Special food that contains human food ingredients suc as M. sylvestris was fed to pets to treat atopic dermatitis: positive results 327

Multiple activity
Leaves ethanolic extract was prepared and fractionated with n-hexane, chloroform and ethyl acetate.The extract and fractions were tested for anti-inflammatory, anti-osteoclastogenic and antioxidant activities in vitro and in vivo 328  329 Another two novel polysaccharides were isolated and characterized: L-arabinose, D-galactose and D-mannose (14:28:1, MW= 57000); D-glucose, Dgalactose and D-mannose (10:1:1, MW= 10400). 330Peptidolycan was isolated from seeds and analyzed to reslt 43 % polysaccharide and 57 % protein, with total molecular weight of 22000 kD.The detailed amino acid composition is reported (page 2791) and the polysaccharide is composed of L-arabinose, D-xylose, D-galactose, L-rhamnose and D-galacturonic acid (6:5:3:8:24). 331Branched acidic polysaccharide was isolated from seeds.It cosists mainly of arabinose, xylose, galactose and galacturonic acid, and has phagocytic activity. 332Seven polysaccharides and peptidogylcans were isolated from seeds, and some of them showed anti-complementary and hypoglycemic activities. 333ovel acidic polysaccharide was isolated from seeds, and it showed phagocytic and anticomplementary activities (L-arabinose, D-xylose, D-galactose, D-glucose, L-rhamnose and Dgalacturonic acid (30:15:20:3:2:10, MW= 26000). 334A neutral, branched polysaccharide was isolated and analyzed by chemical and enzymatic tools (glucose, galactose and arabinose), and it showed phagocytic activity 335 Branched acidic polysaccharide was isolated and analyzed showing anticomplementary activity. 336Branched acidic polysaccharide was isolated from seeds, and it has phagocytic activity. 337

Heavy metals accumulation
Compared with three other plants, M. verticillata was found to be moderate toxic metals accumulator, even though Cd accumulation was highest in some samples. 338Out of four plants, M. verticillata was found to be good metal accumulator in average, and highets for both Cd and Pb. 339ntimicrobial, antidiabetic, antibacterial Leaves methanolic and n-hexane extract were prepared.Methanolic extract which contained mainly steroids and flavonoids, showed moderate activity against E. Bacillus, S. coli and S. aureus, while hexane extract showed moderate activity against the first two bacteria.340Seeds were extracted with ethanol followed by fractionation with n-hexane, chloroform, ethylacetate, n-butanol and water.The original extract had significant antidiabetic activity.Among the fractions, the hexanic had the highest activity. 341Leaves methanolic extract was tested against alloxan-induced diabetes in rats:high.70 % Methanol (water) leaves extract was tested against eleven bacteria species: inactive. 342Leaves methanolic extract was tested for glucose-lowering activity in rats:high. 343ntioxidant, antiinflammatory, anti-dermatitis 80 % Methanolic (water) extract (plant part not indicated) was tested for antioxidant activity by two methods (moderate) and total phenolic content (low). 344Seeds were extracted with seeds or other parts of seven additional plats.The extract found to be anti-inflammatory, heme oxygenase-1 inhibitor and immunomodulatory. 345Hydrodistillation of leaves yielded an oil that found active against LPS induces dermatitis. 346Leaves aqueous extract found active against ulcerative inflammation induced by reserpine in mice. 347Seed ethanolic extract was fractionated with methylene chloride, ethyl acetate and water.The extract and the fractions were tested in Wnt/catenin reporter activity assay.It modulated the -catenin pathway of dermal papilla cells. 348

Osteoclastogenesis and bone resorption supression
Seed aqueous extract inhibited osteoclastogenesis stimulated by receptor activator of nuclear factor-kB.The extract was analyzed by GCMS and 14 compounds were identified.Authors conclude that medicinal activity should be related to synergims of compounds. 349(see note after this reference).

New compounds
Seeds were extracted with ethanol followed by fractionation with methylene chloride extract, ethyl acetate and water.Each fraction was analyzed by liquid chromatography and a new compound was isolated: verticilloside, 3-O-[β-D-(6'-linoleoyl)glucopyranosyl]-β-sitosterol (see Figure 9). 351Leaves were extracted successively with petroleum ether and ethyl acetate.Two new compounds were isolated (Figure 9) and tested for antibacterial activity. 352If the inconsistency of references 261 and 263 can be ignored, Malva species as living plants or as fabricated sieves, can be used for removal of heavy metals from soil or water.It is also clear that Malva species are successful cadmium and lead accumulators.
Many of the studies that we cited here report antimicrobial, antibacterial and/or antifungal activities.Among those, it is interesting to notice the contradiction between the data reported in references 270 and 271: while the first reports the antifungal activity of M. sylvestris tincture, the second found no antimicrobial activity of the plant tincture, which is a component of commercial mouthwash.Despite this, the antibacterial, antimicrobial and antifungal activities of Malva species are proven beyond any doubt (see tables 6-9).
One of the interesting reports of the uses of M. sylvestris in herbal-traditional medicine, was published by S. G. Oliviera et al. in 2015. 317They indicated that about 87 % of their study sample of people, reported the use of this plant and its products along with allopathic medicines or without them.Authors warn (page 5) that people are unaware of the plant possible toxicity, citing M. R. Ritter et al. 370 But reading carefully the publication of M. R. Ritter shows that there is no mentioning of M. sylvestris toxicity.Moreover, it was shown by Consolini & Ragone, that this plant is completely safe for all potential uses. 371 recent decades, there is growing interest in reducing damages of synthetic drugs by using natural plant extracts or other plant products.Among these synthetic drugs and chemicals, both organic, but mainly inorganic chemicals are widely used, and have some severe adverse effects. 372,373A. A. Ben Saad and his colleagues, presented very promising results of using M. sylvestris aqueous extract to reduce the side effect of lithium carbonate. 319,320Similar reports were published by other groups.For example, petroleum ether extract of Solanum trilobatum has a protective effect against lithium carbonate, 374 but unlike M. sylvestris that is soft to touch and completely safe, 375 S. trilobatum is a thorny plant and mildly toxic.The same Tunisian group of A. Ben Saad et al. is searching for other plants that can ameliorate damages of lithium carbonate, and recently they have published the positive results of their study of juice of Opuntia ficus-indica (cactus) thorny cladodes. 376e of Malva species for constipation relief is known in most traditional medicines of Asia (M.neglecta 36,41,52,59 , M. parviflora 67 and M. sylvestris 108,110,115 ).This activity is recently investigated by several groups.One of the interesting reports was published by a M-A.Jabri and his colleagues. 323They induced constipation in rats by loperamide (Figure 8), a synthetic alkaloid, usually marketed as the commercial Imodium for diarrhea relief.Constipation was successfully treated with aqueous extract of M. sylvestris leaves.As control laxative, they used yohimbine (Figure 8), naturally occurring major alkaloid found in the bark of Pausinystalia johimbe. 377e anti-constipation activity of M. sylvestris leaves extract explained by the authors as a result of the antioxidant capacity, and they present possible mechanism of action (page 6).M. Elsagh et al. reported the successful use of flowers aqueous extract for the same goal. 322Since both leaves and flowers of this plant are flavonoid-rich, these results of these two reports are consistent.
The presence of polysaccharides in Malva species drew the much attention from research groups.The isolated and characterized (fully or partially) polysaccharides were also tested for various activities viz., M. aegyptiaca, 133 M. mohileviensis (anti-inflammatory, antioxidant), 143 M. pussila (anti-inflammatory), 149 M. sylvestris (anti-complementary, 220 antioxidant, 222 anti-ulcerative, antimicrobial, antitumor and antioxidant [300][301][302] ).All polysaccharides in these species are acidic, containing glycoronic acids, and relatively, water soluble.Polysaccharides isolated from seeds of M. verticillata are neutral, 329,330 and acidic with high acid content. 331Later on, this Japanese group reported that some of these acidic polysaccharides (or peptidoglycans) have medicinal activities such as phagocytic, 332,337 anticomplementary and hypoglycemic, 333 phagocytic and anticomplementary, 334 and anti-complementary. 336Phagocytic activity was also found in the neutral polysaccharide. 335This extensive study that was done with M. verticillata should be done with other common Malva species.
Treating hair loss with Malva species products is known from traditional medicine of Iraq (M.parviflora), 73 and Iran (M.sylvestris). 115Modern research confirmed these uses and E. Y. Lee et al. report that M. verticillata ethanolic extract and its fractions are modulating the Wnt/-catenin pathway of dermal papilla cells, and thus, it's a good candidate for treating hair loss. 348Their analysis revealed that the active compound is myristoleic acid (C14: 1 cis 9).Another medicinal property that is known to traditional medicine and was confirmed lately by modern research is the ability of Malva extracts to repair bones.M. neglecta is used in traditional medicine of India (leaves), 26 and Turkey (whole plant), 41 to repair fractured bones.K-S.Shim et al. from Korea, report that water extract of M. verticillata suppresses osteoclastogenesis and bone resorption. 349 verticillata is still providing modern research with new and very interesting compounds.One of these compounds was isolated and characterized by and her colleagues from ethanolic extract of the plant: verticilloside (Figure 9).351 Another two new compounds were isolated from leaves extract: tetracontanyl palmitate (C56H112O2) and a waxy ketone (Figure 9), but the exact structure of the ketone was not completely elucidated.352

Conclusions
While studying the vast mass of publications about the genus Malva, we reached some important understandings that must be conveyed to interested readers.Some of these publications are inaccurate, to say the least (reference 71 and others).Moreover, some publications do not report any new findings of plants of Malva genus.M. Ishtiaq and his colleagues report an ethnomedicinal survey of the plants of Samahni valley in Pakistan. 378In fact, there is no new information at all about M. parviflora, which is listed there, and for this reason, it was not included in table 2. Same consideration was taken for the report of Jeambey et al from Lebanon. 379They cite previous reports and plants consumption as food (M.sylvestris), but again, no real information was provided concerning health or medicinal use of this plant.
During the writing itself, we discovered a strange fact: despite being one of the most useful species of Malva, M. nicaeensis was very poorly studied for medicinal-biological activities.It is widespread in the Middle East, especially in the Western part of it, and it is used as food in various ways (see table 4).It is also worth noticing that compared with other major Malva species, its traditional medicinal uses were very partially reported.Such reports were lately published.
M. Mosaddegh and his colleagues from Iran report that its roots and flowers decoction is traditionally used to treat stomach pains.380Nasab & Khosravi (Iran) present the ethnomedicinal use of M. nicaeensis, along with M. parviflora and M. sylvestris.381Its fruits decoction is used to treat cold and sore throat.S. Baydoun and her colleagues from Lebanon report that leaves decoction to have several uses to treat: catarrhs, renal infections, kidney stones, respiratory infections, constipation and skin diseases. 382trangely enough, only three reports were published about medicinal activities of this plant, [146][147][148] and its chemical composition, partial or complete, was never published.Moreover, for other major species, some same activities were reported by many groups or the same group more than once: antioxidant, antibacterial, anti-inflammatory.These activities were never published for M. nicaeensis.
Our group is currently working on these studies.Therefore, we conclude and recommend: (1) There is a need for extensive, systematic study of M. nicaeensis.
(2) Contradicting reports of medicinal activities of Malva species must be resolved by follow up studies.
(3) Proven and very useful medicinal activities of Malva species (antidiabetic, antiobesity) must draw more attention of researchers to convert this potential to practical drug treatments.
(4) It is very important to re-evaluate contradicting and inaccurate reports by further studies.
(5) It is important and useful to isolate the natural product/s responsible for medicinal activities of the plants, and study the mechanism of action.This can open a window of improving the activity.

Table 1 .
Traditional uses of M. neglecta.

Table 5 .
Modern research findings of some Malva species.

Table 7 .
Modern research findings of Malva parviflora.

Table 8 .
Modern research findings of Malva sylvestris.
145ibacterialHexane, dichloromethane and methonal extracts were prepared then the dry matter was suspended in DMSO.Its antibacteria activity was very weak144Plant pigmentsChlorophylls and carotenoids were isolated and identified145AntibacterialAqueous, ethanolic and chloroform extracts of M. neglecta and M. sylvestris were tested against seven types of bacteria that cause wound infections.All extracts were active, and ethanolic was most active for both plants.Extract of M. sylvestris was more efficient 161 Flavonoid glucoronides

Table 9 .
Modern research findings of Malva verticillata

Table 10 .
Reported heavy/toxic metals accumulation capacity of Malva species.