Antiinflammatory,Antioxidant, and Immunomodulatory Effects of Crocus sativus L. and its Main Constituents

Crocus sativus L. (C. sativus), commonly known as saffron, is used as a food additive, preservative, and medicinal herb. Traditionally, it has been used as an alternative treatment for different diseases. C. sativus' medicinal effects are related to its major constituents like crocins, crocetin, and safranal. According to the literature, C. sativus and its constituents could be considered as an effective treatment for neurodegenerative disorders, coronary artery diseases, asthma, bronchitis, colds, fever, diabetes, and so on. Recently, numerous studies have reported such medicinal properties and found that the underlying mechanisms of action may be mediated by antioxidant, inflammatory, and immunomodulatory effects. C. sativus enhances the antioxidant capacity and acts as a free radical scavenger. As an antiinflammatory and immunomodulatory agent, it modulates inflammatory mediators, humoral immunity, and cell‐mediated immunity responses. This review highlights in vitro and animal findings regarding antiinflammatory, antioxidant, and immunomodulatory effects of C. sativus and its constituents. Present review found that the C. sativus and its main constituents such as safranal, crocins, and crocetin could be effective against various diseases because of their antioxidant, anti‐inflammation, and immunomodulatory effects. Copyright © 2016 John Wiley & Sons, Ltd.     

Thymol,thyme, and other plant sources: Health and potential uses

Thymol is a naturally occurring phenol monoterpene derivative of cymene and isomer of carvacrol. Thymol (10–64%) is one of the major constituent of essential oils of thyme (Thymus vulgaris L., Lamiaceae), a medicinal plant with several therapeutic properties. This plant, native to Mediterranean regions, is commonly used as a culinary herb and also with a long history of use for different medicinal purposes. Nowadays, thymol and thyme present a wide range of functional possibilities in pharmacy, food, and cosmetic industry. The interest in the formulation of pharmaceuticals, nutraceuticals, and cosmeceuticals based on thymol is due to several studies that have evaluated the potential therapeutic uses of this compound for the treatment of disorders affecting the respiratory, nervous, and cardiovascular systems. Moreover, this compound also exhibits antimicrobial, antioxidant, anticarcinogenesis, anti‐inflammatory, and antispasmodic activities, as well as a potential as a growth enhancer and immunomodulator. In the present review, these bioactivities have been covered because some of them can contribute to explain the ethnopharmacology of thymol and its main source, T. vulgaris. Other important aspects about thymol are discussed: its toxicity and bioavailability, metabolism, and distribution in animals and humans.     

In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone

The aim of this study was to examine in vitro the inhibitory activity exerted by the main constituents of essential oil obtained from the aromatic plant Thymus vulgaris L. on acetylcholinesterase (AChE). The total essential oil and selected compounds, specifically linalool and thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone, were tested for AChE inhibition. Thymohydroquinone exhibited the strongest AChE inhibitory effect over the range of concentrations. The AChE inhibitory potential decreased in the following order: thymohydroquinone > carvacrol > thymoquinone > essential oil > thymol > linalool. It is interesting that the AChE inhibitory effect exerted by carvacrol was 10 times stronger than that exerted by its isomer thymol, although thymol and carvacrol have a very similar structure.     

The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): a short review

The essential oil extracted from the dried flower buds of clove, Eugenia caryophyllata L. Merr. & Perry (Myrtaceae), is used as a topical application to relieve pain and to promote healing and also finds use in the fragrance and flavouring industries. The main constituents of the essential oil are phenylpropanoids such as carvacrol, thymol, eugenol and cinnamaldehyde. The biological activity of Eugenia caryophyllata has been investigated on several microorganisms and parasites, including pathogenic bacteria, Herpes simplex and hepatitis C viruses. In addition to its antimicrobial, antioxidant, antifungal and antiviral activity, clove essential oil possesses antiinflammatory, cytotoxic, insect repellent and anaesthetic properties. This short review addresses the chemical composition and biological effects of clove essential oil, and includes new results from GC/MS analysis and a study of its antimicrobial activity against a large number of multi-resistant Staphylococcus epidermidis isolated from dialysis biomaterials.     

Dittany of Crete: A botanical and ethnopharmacological review

Origanum dictamnus (Lamiaceae family), an endemic plant of the Greek island of Crete, is widely used as a traditional medicine since antiquity, all over Europe. The aim of the present review is to present comprehensive information of the plant's botanical taxonomy and morphology, as well as of the chemical constituents, biological and pharmacological research on O. dictamnus, which will be presented and critically evaluated. The paper also highlights particularly interesting aspects and common medicinal uses not previously described in the specific ethnobotanical literature. An increasing number of chemical and pharmacological studies have been reported recently, some of which strongly support its traditional medicinal uses against various illnesses such as sore throat, cough and gastric ulcer. A variety of compounds, including flavonoids, lipids and terpenoids (mainly carvacrol and thymol) have been identified from the plant. Current studies have showed that the extracts, the essential oil, as well as their active principles possess several pharmacological properties, like antimicrobial, antioxidant and anti-ulcer ones. The recent scientific data and the rich historical evidence of its medicinal uses could support further research as well as its use as a safe herbal medicinal product.     

Phytochemical constituents,biological activities,and health‐promoting effects of the genus Origanum

Origanum species are mostly distributed around the Mediterranean, Euro‐Siberian, and Iran‐Siberian regions. Since time immemorial, the genus has popularly been used in Southern Europe, as well as on the American continent as a spice now known all over the world under the name “oregano” or “pizza‐spice.” Origanum plants are also employed to prepare bitter tinctures, wines, vermouths, beer, and kvass. The major components of Origanum essential oil are various terpenes, phenols, phenolic acids, and flavonoids with predominant occurrence of carvacrol and thymol (with reasonable amounts of p‐cymen and ‐terpinene) or of terpinene‐4‐ol, linalool, and sabinene hydrate. Many species of Origanum genus are used to treat kidney, digestive, nervous, and respiratory disorders, spasms, sore throat, diabetes, lean menstruation, hypertension, cold, insomnia, toothache, headache, epilepsy, urinary tract infections, etc. Origanum essential oil showed potent bioactivities owing to its major constituents' carvacrol, thymol, and monoterpenes. Several preclinical studies evidenced its pharmacological potential as antiproliferative or anticancer, antidiabetic, antihyperlipidemic, anti‐obesity, renoprotective, antiinflammatory, vasoprotective, cardioprotective, antinociceptive, insecticidal, and hepatoprotective properties. Its nanotechnological applications as a promising pharmaceutical in order to enhance the solubility, physicochemical stability, and the accumulation rate of its essential oils have been investigated. However, Origanum has been reported causing angioedema, perioral dermatitis, allergic reaction, inhibition of platelet aggregation, hypoglycemia, and abortion. Conclusive evidences are still required for its clinical applications against human medical conditions. Toxicity analyses and risk assessment will aid to its safe and efficacious application. In addition, elaborate structure–activity studies are needed to explore the potential use of Origanum‐derived phytochemicals as promising drug candidates.     

A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology,toxicology, and some pharmaceutical aspects

Beneficial therapeutic effects of phenolic acids have been proven in various research projects including in vivo and in vitro studies. Gentisic acid (GA) is a phenolic acid that has been associated with useful effects on human health, such as antiinflammatory, antigenotoxic, hepatoprotective, neuroprotective, antimicrobial, and especially antioxidant activities. It is an important metabolite of aspirin and also widely distributed in plants as a secondary plant product such as Gentiana spp., Citrus spp., Vitis vinifera, Pterocarpus santalinus, Helianthus tuberosus, Hibiscus rosa‐sinensis, Olea europaea, and Sesamum indicum and in fruits such as avocados, batoko plum, kiwi fruits, apple, bitter melon, black berries, pears, and some mushrooms. This study was undertaken to review the pharmacological effects, pharmacokinetic properties as well as toxicity and pharmaceutical applications of GA.     

Rhodiola rosea L. and Alzheimer's Disease: From Farm to Pharmacy

Rhodiola rosea L. (roseroot) is a common member of the family Crassulaceae, known as one of the most important popular medicinal plants in the northern region of Europe. The roots of R. rosea possess a wide range of pharmacological activities such as antioxidant, antiinflammatory, anticancer, cardioprotective, and neuroprotective effects that are because of the presence of different phytochemicals such as phenols and flavonoids. In addition, the presence of salidroside, rosavins, and p‐tyrosol are responsible for its beneficial effects for the treatment of on depression, fatigue, and cognitive dysfunction. A plethora of studies report that R. rosea has potent neuroprotective effects through the suppression of oxidative stress, neuroinflammation, and excitotoxicity in brain tissues and antagonism of oncogenic p21‐activated kinase. However, to our knowledge, no review articles have been published addressing the neuroprotective effects of R. rosea. Therefore, the present article aims at critically reviewing the available literature on the beneficial effects of R. rosea on as a therapeutic strategy for the treatment of Alzheimer's disease and other neurodegenerative diseases where oxidative stress plays a major role in disease development and progression. We also discuss the cultivation, phytochemistry, clinical impacts, and adverse effects of R. rosea to provide a broader insight on the therapeutic potential for this plant. Copyright © 2016 John Wiley & Sons, Ltd.     

Review of the Pharmacological Effects of Vitis vinifera (Grape) and its Bioactive Constituents: An Update

Vitis vinifera fruit (grape) contains various phenolic compounds, flavonoids and stilbenes. In recent years, active constituents found in the fruits, seeds, stems, skin and pomaces of grapes have been identified and some have been studied. In this review, we summarize the active constituents of different parts of V. vinifera and their pharmacological effects including skin protection, antioxidant, antibacterial, anticancer, antiinflammatory and antidiabetic activities, as well as hepatoprotective, cardioprotective and neuroprotective effects in experimental studies published after our 2009 review. Clinical and toxicity studies have also been examined. Copyright © 2016 John Wiley & Sons, Ltd.     

Effect of Trimeric Myricetin Rhamnoside (TMR) in Carrageenan‐induced Inflammation and Caecal Ligation and Puncture‐induced Lung Oxidative Stress in Mice

The Eugenia jambolana is used in folklore medicine. Leaves of E. jambolana contain flavonoids as their active constituents which possess in vitro antiinflammatory, antioxidant and the antimicrobial activity. The aim of the present study was to investigate the antiinflammatory and antioxidant effects of a flavonoid glucoside, trimeric myricetin rhamnoside (TMR) isolated from leaves of E. jambolana. TMR was studied for antiinflammatory activity in carrageenan‐induced hind paw oedema and antioxidant activity in lung by caecal ligation and puncture (CLP)‐induced sepsis in mice. Results of the present study indicated that TMR significantly attenuated the oedema, myeloperoxidase (MPO), cytokines and prostaglandin levels in the paw after 5 h of carrageenan injection as compared to vehicle control. It also reduced the lung MPO, lipid peroxides, and serum nitrite plus nitrate levels and increased lung reduced glutathione levels 20 h of CLP as compared to vehicle control. Thus the results of this study concluded that the TMR appears to have potential benefits in diseases that are mediated by both inflammation and oxidative stress and support the pharmacological basis of use of E. jambolana plant as traditional herbal medicine for the treatment of inflammatory diseases. Copyright © 2015 John Wiley & Sons, Ltd.     

One Plant,Many Uses: A Review of the Pharmacological Applications of Morinda citrifolia

Morinda citrifolia, also known as noni, is commonly used in popular medicine in Brazil. Many parts of the noni tree are utilized in such practices, including the roots, leaves and seeds. Through a search of online databases, the present article reviews 92 research studies on the biological actions of M. citrifolia. The paper will discuss the therapeutic effects of noni and its compounds in a variety of forms of presentation, focusing on studies that support its traditional use. A large and diverse number of properties were identified, which were divided into immunostimulatory, antitumor, antidiabetic, anti‐obesity, antibacterial and anti‐septic, antifungal, antiviral, leishmanicidal, antiinflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, antiangiogenic, antiemetic and anti‐nausea, anti‐gastric ulcer and oesophagitis, anthelmintic, antimutagenic, antipsychotic, anxiolytic, photoprotective, anti‐wrinkle and periodontal tissue regeneration activities. While it was concluded that although M. citrifolia is widely and successfully used for the treatment or prevention of various diseases, it should be consumed carefully, and only after exhaustive studies into its chemical constituents and mechanisms of action, both in in vitro and in vivo models, as well as clinical trials. Copyright © 2017 John Wiley & Sons, Ltd.     

Pharmacological and chemical features of Nepeta L. genus: Its importance as a therapeutic agent

Medicinal plants have always had great value for the human population due to their valuable constituents and potential bioactivities. The objective of this review is to present an updated overview of an important medicinal plant genus Nepeta L., from the family Lamiaceae, revealing its traditional utilization, biological activity, phytoconstituents, and mechanisms of action. For this purpose, a literature survey was carried out by using SciFinder, ScienceDirect, Scopus, PubMed, and Web of Science followed by a revision of the bibliographies of the related articles. We have described and analyzed the role of plants in drug discovery and the importance of Nepeta species. Information on the utilization purposes of Nepeta species in folk medicine has been emphasized, and scientific studies on the biological effects and secondary metabolites are addressed. Nepeta species are characterized by terpenoid‐type compounds and phenolic constituents, which exert several activities such as an antimicrobial, repellent against major pathogen vector mosquitoes, insecticide, larvicide against Anopheles stephensi, cytotoxic anticarcinogen, antioxidant, anticonvulsant, analgesic, anti‐inflammatory agent, and antidepressant, revealing its importance in medicinal and agricultural fields. On the basis of numerous studies, the Nepeta genus demonstrates remarkable therapeutic effects against various diseases. However, clinical studies are warranted to confirm preclinical findings.     

Malva species: Insights on its chemical composition towards pharmacological applications

Malvaceae family is typical from the Mediterranean region, contains 240 genera and more than 4,200 species. They are most commonly used as ornamental plants, although they can also be conceived as a food resource and remedy for various diseases, such as digestive, respiratory, genitourinary, throat infections, and skeletal and skin disorders, as also injuries where they are profoundly applied for skin care and as antiseptic and demulcent. They also possess diuretic, lenitive, spasmolytic, and laxative effects, besides to be used as antidiarrheal. Thus, the present review provides in‐depth data on Malva spp. potential applications and phytochemical composition for food and pharmaceutical industries. Habitat and cultivation conditions and the clinical reports related to its biological effects are also emphasized. Malva spp. possess a wide variety of chemical constituents (such as polysaccharides, coumarins, flavonoids, polyphenols, vitamins, terpenes, and tannins) found in different plant organs, especially in leaves and flowers, connected to their biological activity. In general, Malva spp. have rather moderate antimicrobial activity, high antiinflammatory and wound healing activities, strong antioxidant activity, and anticancer properties. Results from in vitro and in vivo experiments encourage more in‐depth studies, namely clinical trials, towards to improve knowledge on the use of Malva spp. for the treatment of various health conditions in humans.     

Antiinflammatory and anti‐cancer activities of pomegranate and its constituent,ellagic acid: Evidence from cellular,animal, and clinical studies

Inflammation is commonly characterized as a defensive and protective reaction of the body to various exogenous or endogenous stimuli, which aims to maintain the body health. Punica granatum (pomegranate) and its constituent ellagic acid (EA) are recently more taken into accounts since their promising pharmacological effects. Therefore, we aimed to obtain a comprehensive review regarding antiinflammatory, anticancer, and antioxidant activities of both pomegranate and EA and their possible involved mechanisms. In the procedure, scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar, were searched in the English language, until the end of January 2019. Pomegranate belonging to the Punicaceae has been used for medical purposes from ancient and in different cultures. Several studies have also supported that EA is the major active compound of pomegranate and possesses antimutagenic, antiinflammatory, antifibrosis, anticancer, and antiaging properties. It has been suggested that pomegranate and EA possess promising immunomodulatory effects in preclinical models as well as human studies through regulation of the T‐cell function and suppressing humoral immunity. Hopefully, we wish that this review and information could be helpful for designing further experiments to investigate the potential protective effects of pomegranate and EA.     

Topical Antiinflammatory Activity of Essential Oil of Lippia sidoides Cham: Possible Mechanism of Action

This work reports the chemical composition of the essential oil of Lippia sidoides (EOLS) and evaluation of the topical effect of EOLS and thymol against different irritant agents in vivo. The essential oil was obtained by hydrodistillation, and gas chromatography/mass spectrometry analysis identified the main constituents: thymol (84.9%) and p‐cymene (5.33%). The antiinflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, phenol or histamine, and chronic inflammation induced by croton oil. The topical application of EOLS or thymol at a dose of 2 mg/ear significantly reduced (p < 0.001) ear edema induced with arachidonic acid by 45.1% and 47.4% and reduced ear edema induced with phenol by 33.2% (p < 0.05) and 54.7% (p < 0.01) in acute ear edema. However, a proinflammatory effect of EOLS and thymol was evidenced when it was applied for more than 1 day. There were no statistical differences in antiedematogenic activity between EOLS and thymol. In conclusion, the results indicate that thymol is the constituent responsible for the topical antiinflammatory activity of EOLS. Thus, these findings could justify the popular use of L. sidoides by alternative medicine, but chronic use has an inflammatory effect. Copyright © 2012 John Wiley & Sons, Ltd.     

Phytochemistry and Medicinal Properties of Teucrium polium L. (Lamiaceae)

Teucrium polium L. (family Lamiaceae) is a wild‐growing flowering plant, found abundantly in South‐Western Asia, Europe and North Africa. Traditionally, T. polium has been used for different pathological conditions such as gastrointestinal disorders, inflammations, diabetes and rheumatism. In traditional Iranian medicine (TIM), the tea of T. polium is used for treating many diseases such as abdominal pain, indigestion, common cold and type 2 diabetes. Based on this background, many studies have been followed for scientific confirmation of the above‐mentioned properties. In this review, 100 articles published from 1970 to 2011 in the area of phytochemistry, pharmacology and toxicology of extracts and compounds isolated from T. polium have been evaluated. During the past 40 years, different classes of compounds have been isolated from various parts of T. polium of which the main groups are terpenoids and flavonoids. It has been found that these compounds possess a broad spectrum of pharmacological effects including antioxidant, anticancer, antiinflammatory, hypoglycemic, hepatoprotective, hypolipidemic, antibacterial and antifungal. The results of data analyses on the chemical, pharmacological and toxicological characteristics of T. polium support the view that this plant has beneficial therapeutic properties. However, further studies to identify the active components and further verify their relevant pharmacological activities are warranted. Copyright © 2012 John Wiley & Sons, Ltd.     

A Pharmacological Review of Bioactive Constituents of Paeonia lactiflora Pallas and Paeonia veitchii Lynch

The roots of two peony species, Paeonia lactiflora Pallas and Paeonia veitchii Lynch are routinely referred to as either chishao (赤芍) or baishao (白芍). This paper reviews the botanical origins and traditional medicinal usage of each species, as well as pharmacological like activity of their constituents. A search of herbal pharmacological encyclopaedia, PubChem and PubMed databases identified their known constituents. The biological data for these constituents were evaluated and classified according to pharmacological‐like activity, with emphasis on compounds of greatest concentration and bioavailability. It was found that P. lactiflora and P. veitchii have some common compounds; however, their phytochemical bioavailability varies. Furthermore, a larger number of compounds have been identified in P. lactiflora. These have greater potential for antiinflammatory, antiviral, antibacterial and antioxidant therapeutic activity compared with P. veitchii. However, evidence indicates both species are similarly indicated for antiviral and glycaemic activity. Major compounds of each are classified as flavonoids, hydrolysable tannins (polyphenols) and monoterpene glycosides. The evidence suggests both species, when administered in entire botanical form, have an excellent safety profile; however, constituent toxicity risk evidence is limited, requiring further investigation. Although experiments show many compounds have biological activity, further investigation of their therapeutic potential is needed. Copyright © 2016 John Wiley & Sons, Ltd.     

Pharmacological Effects of Capparis spinosa L.

Medicinal plants have been known as one of the most important therapeutic agents since ancient times. During the last two decades, much attention has been paid to the health‐promoting effects of edible medicinal plants, because of multiple beneficial effects and negligible adverse effects. Capparis spinosa L. is one of the most common medicinal plants, used widely in different parts of the world to treat numerous human diseases. This paper aims to critically review the available scientific literature regarding the health‐promoting effects of C. spinosa, its traditional uses, cultivation protocols and phytochemical constituents. Recently, a wide range of evidence has shown that this plant possesses different biological effects, including antioxidant, anticancer and antibacterial effects. Phytochemical analysis shows that C. spinosa has high quantities of bioactive constituents, including polyphenolic compounds, which are responsible for its health‐promoting effects, although many of these substances are present in low concentrations and significant changes in their content occur during processing. In addition, there is negligible scientific evidence regarding any adverse effects. Different health promotion activities, as well as tremendous diversity of active constituents, make C. spinosa a good candidate for discovering new drugs. However these findings are still in its infancy and future experimental and clinical studies are needed. Copyright © 2016 John Wiley & Sons, Ltd.     

Antiinflammatory Properties of the Stem‐bark of Anopyxis klaineana and its Major Constituent,Methyl Angolensate

Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) is one of the reputed West African folkloric medicines that has never been investigated for its pharmacological effects or phytochemical constituents. In the present study, the antiinflammatory properties of the stem‐bark extracts were evaluated using the carrageenan‐induced paw oedema model in chicks. The petroleum ether, ethyl acetate and methanol extracts all showed a time and dose‐dependent antiinflammatory effect over the 5‐h observation period. Phytochemical analysis of the most active extract (methanol extract) yielded the principal constituent that was identified as methyl angolensate through extensive spectroscopic and X‐ray analysis studies. Although slightly less potent (ED₅₀, 4.05 ± 0.0034 mg/kg, orally) than the positive control, diclofenac (ED₅₀, 2.49 ± 0.023, intraperitoneally n = 5), this first ever compound isolated from A. klaineana showed promising antiinflammatory activity that may account to some of the reported medicinal uses of the plant. Copyright © 2014 John Wiley & Sons, Ltd.