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.     

A comprehensive review on ethnomedicine,phytochemistry, pharmacology,and toxicity of Tephrosia purpurea (L.) Pers.

Tephrosia purpurea (L.) Pers. is a well‐known plant in Ayurveda and named “Sarwa wranvishapaka” for its property to heal wounds. Traditionally, it is practiced for impotency, asthma, dyspepsia, hemorrhoids, syphilis gonorrhea, rheumatism, enlargement of kidney and spleen. It is an important component of herbal preparations like Tephroli and Yakrifti used to cure liver disorders. Various phytocompounds including pongamol, purpurin, purpurenone, tephrosin, bulnesol, tephrostachin, β‐sitosterol, and so on have been reported. Modern pharmacological studies have shown that the plant have wound healing, antileishmanial, anticarcinogenic, antimicrobial, antioxidant, hepatoprotective, antifertility, antispermatogenic, anti‐diarrheal, diuretic, and insecticidal properties. Acetylcholinesterase inhibitory action reported from this plant aids its utilization for the development of drugs for Alzheimer's and dementia neurological disorders. Among the known active compounds of T. purpurea, tephrostachin is responsible for antiplasmodial activity, tephrosin, pongaglabol, and semiglabrin exerts antiulcer activity while quercetin, rutin, β‐sitosterol, and lupeol are mainly responsible for its anti‐inflammatory and anti‐cancer properties. From different toxicological studies, concentrations up to 2,000 mg/kg were considered safe. The present review comprehensively summarizes the ethnomedicine, phytochemistry, pharmacology, and toxicology of T. purpurea. Further research on elucidation of the structure–function relationship among active compounds, understanding of multi‐target network pharmacology and clinical applications will intensify its therapeutic potential.     

Therapeutic Potential of Polyphenols from Epilobium Angustifolium (Fireweed)

Epilobium angustifolium is a medicinal plant used around the world in traditional medicine for the treatment of many disorders and ailments. Experimental studies have demonstrated that Epilobium extracts possess a broad range of pharmacological and therapeutic effects, including antioxidant, anti‐proliferative, anti‐inflammatory, antibacterial, and anti‐aging properties. Flavonoids and ellagitannins, such as oenothein B, are among the compounds considered to be the primary biologically active components in Epilobium extracts. In this review, we focus on the biological properties and the potential clinical usefulness of oenothein B, flavonoids, and other polyphenols derived from E. angustifolium. Understanding the biochemical properties and therapeutic effects of polyphenols present in E. angustifolium extracts will benefit further development of therapeutic treatments from this plant. Copyright © 2016 John Wiley & Sons, Ltd.     

Review of Garcinia mangostana and its Xanthones in Metabolic Syndrome and Related Complications

Metabolic syndrome is coexistence of abdominal obesity, hyperglycemia, hyperlipidemia and hypertension that causes cardiovascular diseases, diabetes and their complications, low quality and short lifespan. Garcinia mangostana and its xanthones such as α‐mangostin have been shown desirable effects such as anti‐obesity, anti‐hyperglycemic, anti‐dyslipidemia, anti‐diabetic and antiinflammatory effects in experimental studies. Various databases such as PubMed, Scopus and Web of Science with keywords of ‘Garcinia mangostana’, ‘mangosteen’, ‘α‐mangostin’, ‘metabolic syndrome’, ‘hypoglycemic’, ‘antihyperglicemic’, ‘antidiabetic’, ‘hypotensive’, ‘antihypertensive’, ‘atherosclerosis’, ‘arteriosclerosis’ and ‘hyperlipidemia’ have been investigated in this search without publication time limitation. This study reviewed all pharmacological effects and molecular pathways of G. mangostana and its xanthones in the management of metabolic syndrome and its complications in in‐vitro and in‐vivo studies. Based on these studies, mangosteen and its xanthones have good potential to design human studies for controlling and modification of metabolic syndrome and its related disorders such as obesity, disrupted lipid profile, diabetes and its complications. Copyright © 2017 John Wiley & Sons, Ltd.     

Angiogenesis inhibition by a lichen compound olivetoric acid

Lichens have been used in folk medicine for centuries and are symbiotic organisms of fungi and algae that produce unique secondary metabolites. Olivetoric acid is one of these secondary metabolites. In the present study, the effect of olivetoric acid isolated from acetone extract of the lichen Pseudevernia furfuracea (var. ceratea) on angiogenesis was evaluated. It displayed potent anti‐angiogenic activities in vitro: inhibited proliferation of rat adipose tissue endothelial cells (RATECs) and disrupted endothelial tube formation in a dose‐dependent manner. Furthermore, dose‐dependent depolymerization effects of olivetoric acid on F‐actin stress fibers were observed. Decrease in the tube formation of RATECs by olivetoric acid might be explained by a disorganization of the actin cytoskeleton. These findings suggest that olivetoric acid is a new anti‐angiogenic agent and can be developed as a new therapeutic agent for angiogenesis‐related diseases. Copyright © 2009 John Wiley & Sons, Ltd.     

Hypoglycemic and Hypolipidemic Effects of Aloe vera Extract Preparations: A Review

Obesity is considered to be an epidemic disease, and it is associated with several metabolic disorders. Pharmacological treatments currently available are not effective for prolonged treatment duration. So, people are looking toward new therapeutic approach such as herbal ingredients. Since ancient periods, different herbs have been used for remedy purposes such as anti‐obesity, antidiabetes, and antiinflammatory. Among the several herbal ingredients, Aloe vera (Aloe barbadensis Miller) is widely used to curb the metabolic complications. Till date, reports are not available for the side effects of A. vera. Several researchers are used to different solvents such as aqueous solution, alcohol, ethanol, and chloroform for the A. vera extract preparations and studied their hypoglycemic and hypolipidemic effects in animal and human studies. Furthermore, little information was recorded with the active compounds extracted from the A. vera and their anti‐obesity and antidiabetic effects in clinical studies. In this review, we made an attempt to compile all the available literature by using different search engines (PubMed, Scopus, and Google Scholar) on the A. vera extract preparations and the possible mechanism of action involved in carbohydrate and lipid metabolism. Copyright © 2015 John Wiley & Sons, Ltd.     

Psoralea corylifolia L: Ethnobotanical,biological, and chemical aspects: A review

Psoralea corylifolia L. (Leguminosae) is a well‐known traditional medicinal plant used from ancient times for treatment of various ailments. It is widely distributed and an important part of therapeutics in Ayurveda and in Chinese medicines. The aim of this review is to present comprehensive and most up to date report on its ethnobotanical, ethnopharmacological, clinical, phytochemical, and side effects. Studies on the ethnobotanical, ethnopharmacological, clinical, phytochemical, and side effects of P. corylifolia were published until year 2017 and were searched using various scientific databases. The scientific literature searched revealed that these plant species has been extensively investigated in vivo and in vitro for various biological and phytochemical studies. It has cardiotonic, vasodilator, pigmentor, antitumor, antibacterial, cytotoxic, and anti‐helminthic properties and locally used for alopecia, inflammation, leukoderma, leprosy, psoriasis, and eczema. So far, about a hundred bioactive compounds have been isolated from seeds and fruits, and most important compounds identified belongs to coumarins, flavonoids, and meroterpenes groups. This review article summarized the most updated scientific literature on bioactive phytochemical and biological activities of P. corylifolia. This article will be a useful addition to providing information for future research, and more standard clinical trials are needed for the plant to be used as therapeutic agent.     

The Phytochemistry and Pharmacology of Butia sp.: A Systematic Review and an Overview of the Technological Monitoring Process

The Butia sp. are native South America trees, whose fruits are consumed in natura and have significant biological properties; however, trees of this genus plant are in danger of extinction. A systematic review of the literature and a technological overview were carried out to summarize the available evidence on the therapeutic uses and the phytochemical compounds of Butia sp. The following electronic databases were researched: MedLine (PubMed), Web of Science, Scopus, Scielo, and the gray literature. Furthermore, the online system such as the US Patent and Trademark Office, Espacenet, National Institute of Industrial Property, and Google Patents were accessed to obtain patent data. The inclusion criteria were articles that describe either the therapeutic uses of Butia sp. (antimicrobial activity, antioxidant activity, anti‐inflammatory activity, antineoplastic activity) or studies describing phytochemical compounds of Butia sp. A limited amount of manual search was also undertaken. Reference lists were scanned to identify other relevant studies, and requests for unpublished data were conducted to people working in the field. Among 12 papers and 14 patents, 9 complete texts of scientific articles and 1 patent were scrutinised by two reviewers. We concluded that Butia has shown some antioxidant, anti‐inflammatory, and antimicrobial activity, and its use could have important implications for future therapeutic uses. Although there is evidence of pharmacological potential from in vitro studies, clinical studies must be conducted to confirm the effectiveness of Butia sp. The evidence of its therapeutic uses has not been extensively studied yet, and the available evidence still needs further confirmation. Copyright © 2017 John Wiley & Sons, Ltd.     

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

In respect to the enhanced incidence rate of cancer worldwide, studies have focused on cancer therapy using novel strategies. Chemotherapy is a common strategy in cancer therapy, but its adverse effects and chemoresistance have limited its efficacy. So, attempts have been directed towards minimally invasive cancer therapy using plant derived‐natural compounds. Cryptotanshinone (CT) is a component of salvia miltiorrihiza Bunge, well‐known as Danshen and has a variety of therapeutic and biological activities such as antioxidant, anti‐inflammatory, anti‐diabetic and neuroprotective. Recently, studies have focused on anti‐tumor activity of CT against different cancers. Notably, this herbal compound is efficient in cancer therapy by targeting various molecular signaling pathways. In the present review, we mechanistically describe the anti‐tumor activity of CT with an emphasis on molecular signaling pathways. Then, we evaluate the potential of CT in cancer immunotherapy and enhancing the efficacy of chemotherapy by sensitizing cancer cells into anti‐tumor activity of chemotherapeutic agents, and elevating accumulation of anti‐tumor drugs in cancer cells. Finally, we mention strategies to enhance the anti‐tumor activity of CT, for instance, using nanoparticles to provide targeted drug delivery.     

Investigation of rosemary herbal extracts (Rosmarinus officinalis) and their potential effects on immunity

The discovery of new curative drugs and the consumption of natural dietary ingredients with the ability to exhibit immunomodulatory activity is urgently needed to decrease the risk of chronic diseases among the population. Rosmarinus officinalis (Lamiaceae) is an aromatic plant that has been traditionally and medicinally used as a carminative, antispasmodic, painkiller, circulatory tonic, to stimulate hair growth and to improve memory dysfunction. This study aimed to assess the potential effects of rosemary solvent extracts on human immune function. Science Direct, Web of Science, Wiley, Elsevier, PubMed, Scopus, and the Google scholar search engines were used to retrieve relevant information included combinations of “rosemary” or “R. officinalis” with “immune function,” “immunity,” “immune system,” “anti‐inflammatory,” “inflammation,” or “health benefit.” A number of studies have been found a stimulatory effect of rosemary and its active compounds on the immune system in vitro and animal study, but there is a lack of evidence in humans for supporting this. The results demonstrated the potential of rosemary and its main active components as dietary ingredients with immunomodulatory functionality. Human studies should be performed and a double‐blind randomized controlled trial would be ideal.     

Efficacy and Safety of White Willow Bark (Salix alba) Extracts

Willow bark extract has been used for thousands of years as an anti‐inflammatory, antipyretic, and analgesic. In spite of its long history of use, relatively few human and animal studies have been published that confirm anecdotal observations. A small number of clinical studies have been conducted that support the use of willow bark extracts in chronic lower back and joint pain and osteoarthritis. Willow bark extracts also are widely used in sports performance and weight loss products presumably because of anti‐inflammatory and analgesic activities, although no human studies have been published that specifically and directly document beneficial effects. In recent years, various in vitro and animal studies have demonstrated that the anti‐inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor‐α and nuclear factor‐kappa B. Although willow bark extracts are generally standardized to salicin, other ingredients in the extracts including other salicylates as well as polyphenols, and flavonoids may also play prominent roles in the therapeutic actions. Adverse effects appear to be minimal as compared to non‐steroidal anti‐inflammatory drugs including aspirin. The primary cause for concern may relate to allergic reactions in salicylate‐sensitive individuals. Copyright © 2015 John Wiley & Sons, Ltd.     

6‐Acetoxy Cyperene,a Patchoulane‐type Sesquiterpene Isolated from Cyperus rotundus Rhizomes Induces Caspase‐dependent Apoptosis in Human Ovarian Cancer Cells

Cyperus rotundus (Cyperaceae) has been widely used in traditional medicine for the treatment of various diseases, including cancer. Although an anti‐tumour effect has been suggested for C. rotundus, the anti‐tumour effects and underlying molecular mechanisms of its bioactive compounds are poorly understood. The n‐hexane fraction of an ethanol extract of C. rotundus rhizomes was found to inhibit cell growth in ovarian cancer (A2780, SKOV3 and OVCAR3) and endometrial cancer (Hec1A and Ishikawa) cells. Among the thirteen sesquiterpenes isolated from the n‐hexane fraction, some patchoulane‐type compounds, but not eudesmane‐type compounds, showed moderate cytotoxic activity in human ovarian cancer cells. In particular, the patchoulane sesquiterpene 6‐acetoxy cyperene had the most potent cytotoxicity. In this regard, propidium iodide/Annexin V staining and terminal deoxynucleotidyl transferase dUTP (deoxynucleotide triphosphate) nick end labeling assay were performed to study cell cycle progression and apoptosis. 6‐acetoxy cyperene induced apoptosis, as shown by the accumulation of sub‐G1 and apoptotic cells. Furthermore, treatment with 6‐acetoxy cyperene stimulated the activation of caspase‐3, caspase‐8 and caspase‐9 and poly(ADP‐ribose)polymerase in a dose‐dependent manner. Pretreatment with caspase inhibitors neutralized the pro‐apoptotic activity of 6‐acetoxy cyperene. Taken together, these data suggest that 6‐acetoxy cyperene, a patchoulane‐type sesquiterpene isolated from C. rotundus rhizomes, is an anti‐tumour compound that causes caspase‐dependent apoptosis in ovarian cancer cells. Copyright © 2015 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.     

Anti‐HIV‐1 Integrase Activity and Molecular Docking Study of Compounds from Caesalpinia sappan L.

Caesalpinia sappan L. (Caesalpiniaceae) has been traditionally used as blood tonic, expectorant, and astringent by boiling with water. Searching for HIV‐1 integrase (IN) inhibitors from this plant is a promising approach. The EtOH extract of C. sappan and its isolated compounds were tested for their anti‐HIV‐1 IN effect using the multiplate integration assay, and the active compounds were determined for their mechanisms by molecular docking technique. Extraction from the heartwoods and roots of C. sappan led to the isolation of nine compounds. Among the compounds tested, sappanchalcone (2) displayed the strongest effect against HIV‐1 IN with an IC₅₀ value of 2.3 μM followed by protosappanin A (9, IC₅₀ = 12.6 μM). Structure‐activity relationships of compounds from C. sappan were found, in which the vicinal hydroxyl moiety were essential for anti‐HIV‐1 IN effect of compounds 2 and 9 by binding with the amino acid residues Gln148 and Thr66 in the core domain of the HIV‐ 1 IN enzyme, respectively. Copyright © 2015 John Wiley & Sons, Ltd.     

Bioactive Phenylpropanoids,Phenolic Acid and Phytosterol from Landolphia owariensis P. Beauv Stringy Seed Pulp

Landolphia owariensis P. Beauv is economically important for latex/rubber and folklore medicine. Its stringy seed pulp is freely eaten by humans and animals. Thus, L. owariensis stringy seed pulp was extracted serially with hexane and acetone to isolate and characterize its active pharmaceutical ingredients. Solvent/solvent partition and chromatographic separations afforded four bioactive compounds, (E)‐3‐(3,4‐Dihydroxylcinnamoyl)quinic acid [(E)‐Chlorogenic acid], I; (E)‐3‐(3,4‐Dihydroxylcinnamoyl)quinic acid methyl ester [(E)‐Chlorogenic acid methyl ester], II; 3,4‐Dihydroxylbenzoic acid, (Protocatechuic acid), III; and 22,23‐Dihydrostigmaster‐3β‐ol (3β–Sitosterol) (IV). Structures of I, II and III were assigned by combinations of high‐performance liquid chromatography‐ultraviolet‐visible spectroscopy, 1D and 2D nuclear magnetic resonance spectroscopy, high‐performance liquid chromatography–mass spectrometry and reference to published literatures, while compound IV was identified by chemical methods and gas chromatography–mass spectrometry. The phenylpropanoids and phenolic acid (compounds I, II and III) are notable standard antioxidants with confirmed hepatic‐protective activity and other exciting biological activities. Compound IV has been reported to possess anti‐inflammatory activity, anti‐colon cancer action and a cholesterol‐lowering effect. The described compounds are important medicinal constituents of L. owariensis stringy seed pulp, and this is the first major report on the phytochemistry of L. owariensis P. Beauv. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

Ethnopharmacology,phytochemistry, and biotechnological advances of family Apocynaceae: A review

The family Apocynaceae is one of the largest and important families in angiosperm. Several members of this family have medicinal properties and have been in the treatment of various ailments. Most of them are consumed as food by tribal people whereas a few plants are used as source of poison. Members of family Apocynaceae are rich in alkaloids, terpenoids, steroids, flavonoids, glycosides, simple phenols, lactones, and hydrocarbons. Other compounds such as sterols, lignans, sugars, lignans, and lactones have been isolated and systematically studied. Few studies have reported antioxidant, anti‐inflammatory, antimicrobial, and cytotoxic activities of crude extracts as well as single compound(s) isolated from various members of the family Apocynaceae. Holarrhena antidysenterica, Rauvolfia serpentina, Carissa carandas, and Tabernaemontana divaricata are the extensively studied plants in this family. The present review provides a detailed outlook on ethnopharmacology, phytochemistry, and biological activities of selected members of this family. Moreover, it also covers the biotechnological advances used for large‐scale production of bioactive compounds of therapeutic interest along with plant tissue culture‐based approaches for conservation of this medicinally valuable family.     

Safety and toxicity of silymarin,the major constituent of milk thistle extract: An updated review

Milk thistle (Silybum marianum) is a medicinal plant from the Asteraceae family. Silymarin is the major constituent of milk thistle extract and is a mixture of some flavonolignans such as silybin, which is the most active component of silymarin. It is most commonly known for its hepatoprotective effect. Also, studies have shown other therapeutic effects such as anticancer, anti‐Alzheimer, anti‐Parkinson, and anti‐diabetic, so its safety is very important. It has no major toxicity in animals. Silymarin was mutagen in Salmonella typhimurium strains in the presence of metabolic enzymes. Silybin, silydianin, and silychristin were not cytotoxic and genotoxic at concentration of 100 μM. Silymarin is safe in humans at therapeutic doses and is well tolerated even at a high dose of 700 mg three times a day for 24 weeks. Some gastrointestinal discomforts occurred like nausea and diarrhea. One clinical trial showed silymarin is safe in pregnancy, and there were no anomalies. Consequently, caution should be exercised during pregnancy, and more studies are needed especially in humans. Silymarin has low‐drug interactions, and it does not have major effects on cytochromes P‐450. Some studies demonstrated that the use of silymarin must be with caution when co‐administered with narrow therapeutic window drugs.     

Overview of Oroxylin A: A Promising Flavonoid Compound

Oroxylin A is one of the main active components extracted from Scutellariae radix. It has been proved that oroxylin A possesses a broad spectrum of pharmacological functions, including anti‐cancer, antiinflammation, neuroprotective, anti‐coagulation and so on. The pharmacological activity of oroxylin A has been studied in vitro and on animal models, which reflected its promising potency in disease treatment. This review aims to recapitulate the pharmacological function and the molecular mechanisms of oroxylin A, as well as its sources, extraction, synthesis and toxicity study. These data confirmed the therapeutic potential of oroxylin A and provided reference for further development. Copyright © 2016 John Wiley & Sons, Ltd.